Comprehensive Physiology Wiley Online Library

Mechanisms Modulating Skeletal Muscle Phenotype

Full Article on Wiley Online Library


Mammalian skeletal muscles are composed of a variety of highly specialized fibers whose selective recruitment allows muscles to fulfill their diverse functional tasks. In addition, skeletal muscle fibers can change their structural and functional properties to perform new tasks or respond to new conditions. The adaptive changes of muscle fibers can occur in response to variations in the pattern of neural stimulation, loading conditions, availability of substrates, and hormonal signals. The new conditions can be detected by multiple sensors, from membrane receptors for hormones and cytokines, to metabolic sensors, which detect high‐energy phosphate concentration, oxygen and oxygen free radicals, to calcium binding proteins, which sense variations in intracellular calcium induced by nerve activity, to load sensors located in the sarcomeric and sarcolemmal cytoskeleton. These sensors trigger cascades of signaling pathways which may ultimately lead to changes in fiber size and fiber type. Changes in fiber size reflect an imbalance in protein turnover with either protein accumulation, leading to muscle hypertrophy, or protein loss, with consequent muscle atrophy. Changes in fiber type reflect a reprogramming of gene transcription leading to a remodeling of fiber contractile properties (slow‐fast transitions) or metabolic profile (glycolytic‐oxidative transitions). While myonuclei are in postmitotic state, satellite cells represent a reserve of new nuclei and can be involved in the adaptive response. © 2013 American Physiological Society. Compr Physiol 3:1645‐1687, 2013.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Figure 1. Figure 1. The complete panel of sarcomeric MYH genes in mammals with the corresponding protein products and their expression pattern. The evolutionary relationship between MYH genes is indicated in the phylogenetic tree on the left. Spacing and length of the branches do not reflect actual scale in this simplified scheme. Only extrafusal muscle fibers are considered for the expression pattern. §Expression only in some mammalian species. *MYH7b, also referred to as MYH14, is expressed in both slow muscles and heart at the transcript level, but only in extraocular muscles at the protein level (). Scheme, with permission, from ().
Figure 2. Figure 2. Myosin heavy chain isoforms are the determinants of ATPase activity and maximum shortening velocity (Vo) of single muscle fibers and of filament sliding speed (Vf) on purified myosin in vitro motility assay. Fibers expressing specific myosin isoforms (1 or slow, 2A, 2X, and 2B) have been isolated from muscles of five mammalian species: in all species a progressive increase in ATPase rate, shortening velocity and sliding filament velocity from slow () to 2A, 2X, and 2B is detectable. Comparing different species the kinetics parameters vary in inverse proportion to body size. Note that (i) 2B myosin is not expressed in human and (ii) for experimental reasons determinations of ATPase and Vf were not performed for all myosin isoform in each species. Data, with permission, from ().
Figure 3. Figure 3. Cytosolic calcium transients (A) and myofibrillar response to calcium (B) vary among fiber types. Panel A: calcium transients in four different murine fiber types (1 or slow, 2A, 2X, 2B): the amplitude has been normalized to better show the difference in the decline rate. Adapted, with permission, from (). Panel B: pCa‐force curves in four fiber types from the rat diaphragm: note the greater steepness of the curves of the fast fibers and the greater sensitivity to low calcium concentration of slow fibers. Adapted, with permission, from ()
Figure 4. Figure 4. Myogenic and neurogenic control of fiber‐type specification in skeletal muscles. The scheme illustrates the adaptive range of MyHC transformations observed in different muscle systems after experimental interventions aimed at dissecting the relative contribution of neurogenic factors that induce muscle plasticity and intrinsic myogenic constraints that limit the range of possible adaptations. Based on results from () for electrically stimulated fast and slow rat limb muscles (pink and green, respectively), from () and () for reinnervated rat laryngeal (thyroarytenoid, pale blue) muscle, and from () for reinnervated cat jaw muscle (violet). Scheme, with permission, from ().
Figure 5. Figure 5. Summary of some conditions and factors able to induce skeletal muscle hypertrophy and atrophy. Overload: functional overload imposed by elimination of synergistic muscles; unload: muscle unloading induced by hindlimb suspension or in conditions of microgravity.
Figure 6. Figure 6. Summary of some conditions and factors able to modulate the muscle fiber‐type phenotype. CLFS: chronic electrical stimulation applied continuously either via nerve or directly to denervated muscles; overload: functional overload imposed by elimination of synergistic muscles; unload: muscle unloading induced by hindlimb suspension or in conditions of microgravity.
Figure 7. Figure 7. Adaptive response to chronic electrical stimulation of rat fast muscles, underlining the effects of frequency and amount of stimuli delivered to muscles. Force‐frequency curve and twitch time to peak are taken as read out of muscle adaptation. Panel A shows that prolongation of time to peak (i.e., fast to slow transformation) is only induced by low‐frequency stimulation (<20 Hz). Panel B shows that the effect of the amount of stimuli delivered in 24 h is not effective if the frequency of stimulation is not adequately low. Panel C shows the shift to the left (i.e., toward lower fusion frequency) of the force‐frequency curve and the increase of the twitch/tetanus ratio in relation to the frequency of chronic. Those effects are significant only when stimulation rate is below 50 Hz. Modified, with permission, from ()
Figure 8. Figure 8. The role of intracellular calcium in the regulation of muscle size and function. As can be seen, changes in the level of intracellular calcium can have pronounced effects on the size and function of adult skeletal muscle.
Figure 9. Figure 9. Signaling pathways involved in skeletal muscle hypertrophy. The scheme highlights two major pathways, the IGF/Akt and the myostatin/Smad pathways, which converge on mTOR and protein synthesis.
Figure 10. Figure 10. Overview of the different major pathways involved in the transcriptional regulation of muscle plasticity, focusing on the role of PGC‐1α, AMPK, mTOR, and Cn‐NFAT.

Figure 1. The complete panel of sarcomeric MYH genes in mammals with the corresponding protein products and their expression pattern. The evolutionary relationship between MYH genes is indicated in the phylogenetic tree on the left. Spacing and length of the branches do not reflect actual scale in this simplified scheme. Only extrafusal muscle fibers are considered for the expression pattern. §Expression only in some mammalian species. *MYH7b, also referred to as MYH14, is expressed in both slow muscles and heart at the transcript level, but only in extraocular muscles at the protein level (). Scheme, with permission, from ().

Figure 2. Myosin heavy chain isoforms are the determinants of ATPase activity and maximum shortening velocity (Vo) of single muscle fibers and of filament sliding speed (Vf) on purified myosin in vitro motility assay. Fibers expressing specific myosin isoforms (1 or slow, 2A, 2X, and 2B) have been isolated from muscles of five mammalian species: in all species a progressive increase in ATPase rate, shortening velocity and sliding filament velocity from slow () to 2A, 2X, and 2B is detectable. Comparing different species the kinetics parameters vary in inverse proportion to body size. Note that (i) 2B myosin is not expressed in human and (ii) for experimental reasons determinations of ATPase and Vf were not performed for all myosin isoform in each species. Data, with permission, from ().

Figure 3. Cytosolic calcium transients (A) and myofibrillar response to calcium (B) vary among fiber types. Panel A: calcium transients in four different murine fiber types (1 or slow, 2A, 2X, 2B): the amplitude has been normalized to better show the difference in the decline rate. Adapted, with permission, from (). Panel B: pCa‐force curves in four fiber types from the rat diaphragm: note the greater steepness of the curves of the fast fibers and the greater sensitivity to low calcium concentration of slow fibers. Adapted, with permission, from ()

Figure 4. Myogenic and neurogenic control of fiber‐type specification in skeletal muscles. The scheme illustrates the adaptive range of MyHC transformations observed in different muscle systems after experimental interventions aimed at dissecting the relative contribution of neurogenic factors that induce muscle plasticity and intrinsic myogenic constraints that limit the range of possible adaptations. Based on results from () for electrically stimulated fast and slow rat limb muscles (pink and green, respectively), from () and () for reinnervated rat laryngeal (thyroarytenoid, pale blue) muscle, and from () for reinnervated cat jaw muscle (violet). Scheme, with permission, from ().

Figure 5. Summary of some conditions and factors able to induce skeletal muscle hypertrophy and atrophy. Overload: functional overload imposed by elimination of synergistic muscles; unload: muscle unloading induced by hindlimb suspension or in conditions of microgravity.

Figure 6. Summary of some conditions and factors able to modulate the muscle fiber‐type phenotype. CLFS: chronic electrical stimulation applied continuously either via nerve or directly to denervated muscles; overload: functional overload imposed by elimination of synergistic muscles; unload: muscle unloading induced by hindlimb suspension or in conditions of microgravity.

Figure 7. Adaptive response to chronic electrical stimulation of rat fast muscles, underlining the effects of frequency and amount of stimuli delivered to muscles. Force‐frequency curve and twitch time to peak are taken as read out of muscle adaptation. Panel A shows that prolongation of time to peak (i.e., fast to slow transformation) is only induced by low‐frequency stimulation (<20 Hz). Panel B shows that the effect of the amount of stimuli delivered in 24 h is not effective if the frequency of stimulation is not adequately low. Panel C shows the shift to the left (i.e., toward lower fusion frequency) of the force‐frequency curve and the increase of the twitch/tetanus ratio in relation to the frequency of chronic. Those effects are significant only when stimulation rate is below 50 Hz. Modified, with permission, from ()

Figure 8. The role of intracellular calcium in the regulation of muscle size and function. As can be seen, changes in the level of intracellular calcium can have pronounced effects on the size and function of adult skeletal muscle.

Figure 9. Signaling pathways involved in skeletal muscle hypertrophy. The scheme highlights two major pathways, the IGF/Akt and the myostatin/Smad pathways, which converge on mTOR and protein synthesis.

Figure 10. Overview of the different major pathways involved in the transcriptional regulation of muscle plasticity, focusing on the role of PGC‐1α, AMPK, mTOR, and Cn‐NFAT.
 1.Abrams RA, Tsai AM, Watson B, Jamali A, Lieber RL. Skeletal muscle recovery after tenotomy and 7‐day delayed muscle length restoration. Muscle Nerve 23: 707‐714, 2000.
 2.Adams G, Caiozzo V, Baldwin K. Skeletal muscle unweighting: Spaceflight and ground‐based models. J Appl Physiol 95: 2185‐2201, 2003.
 3.Adams G, Hather B, Baldwin K, Dudley G. Skeletal muscle myosin heavy chain composition and resistance training. J Appl Physiol 74: 911‐915, 1993.
 4.Adams GR, Haddad F, Bodell PW, Tran PD, Baldwin KM. Combined isometric, concentric, and eccentric resistance exercise prevents unloading‐induced muscle atrophy in rats. J Appl Physiol 103: 1644‐1654, 2007.
 5.Aguilar V, Alliouachene S, Sotiropoulos A, Sobering A, Athea Y, Djouadi F, Miraux S, Thiaudiere E, Foretz M, Viollet B, Diolez P, Bastin J, Benit P, Rustin P, Carling D, Sandri M, Ventura‐Clapier R, Pende M. S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase. Cell Metab 5: 476‐487, 2007.
 6.Akimoto T, Sorg BS, Yan Z. Real‐time imaging of peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha promoter activity in skeletal muscles of living mice. Am J Physiol Cell Physiol 287: C790‐C796, 2004.
 7.Allen DL, Loh AS. Posttranscriptional mechanisms involving microRNA‐27a and b contribute to fast‐specific and glucocorticoid‐mediated myostatin expression in skeletal muscle. Am J Physiol Cell Physiol 300: C124‐C137, 2011.
 8.Allen DL, Roy RR, Edgerton VR. Myonuclear domains in muscle adaptation and disease. Muscle & nerve 22: 1350‐1360, 1999.
 9.Amthor H, Otto A, Vulin A, Rochat A, Dumonceaux J, Garcia L, Mouisel E, Hourde C, Macharia R, Friedrichs M, Relaix F, Zammit PS, Matsakas A, Patel K, Partridge T. Muscle hypertrophy driven by myostatin blockade does not require stem/precursor‐cell activity. Proc Natl Acad Sci U S A 106: 7479‐7484, 2009.
 10.Andersen H, Nielsen S, Mogensen CE, Jakobsen J. Muscle strength in type 2 diabetes. Diabetes 53: 1543‐1548, 2004.
 11.Andersen JL, Schjerling P, Saltin B. Muscle, genes and athletic performance. Sci Am 283: 48‐55, 2000.
 12.Anderson E, Neufer P. Type II skeletal myofibres possess unique properties that potentiate mitochondrial H2O2 generation. Am J Physiol Cell Physiol 290: C844‐C851, 2006.
 13.Andersson DC, Betzenhauser MJ, Reiken S, Meli AC, Umanskaya A, Xie W, Shiomi T, Zalk R, Lacampagne A, Marks AR. Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging. Cell metabolism 14: 196‐207, 2011.
 14.Andres‐Mateos E, Brinkmeier H, Burks TN, Mejias R, Files DC, Steinberger M, Soleimani A, Marx R, Simmers JL, Lin B, Finanger Hedderick E, Marr TG, Lin BM, Hourde C, Leinwand LA, Kuhl D, Foller M, Vogelsang S, Hernandez‐Diaz I, Vaughan DK, Alvarez de la Rosa D, Lang F, Cohn RD. Activation of serum/glucocorticoid‐induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy. EMBO Mol Med 5: 80‐91, 2013.
 15.Aragones J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez‐Juan A, Harten SK, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi‐Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P. Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nature Genet 40: 170‐180, 2008.
 16.Arany Z, Foo SY, Ma Y, Ruas JL, Bommi‐Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM. HIF‐independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC‐1alpha. Nature 451: 1008‐1012, 2008.
 17.Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM. The transcriptional coactivator PGC‐1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 5: 35‐46, 2007.
 18.Aravamudan B, Mantilla CB, Zhan WZ, Sieck GC. Denervation effects on myonuclear domain size of rat diaphragm fibers. J Appl Physiol 100: 1617‐1622, 2006.
 19.Arber S, Halder G, Caroni P. Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 79: 221‐231, 1994.
 20.Ausoni S, Gorza L, Schiaffino S, Gundersen K, Lomo T. Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles. J Neurosci 10: 153‐160, 1990.
 21.Bacou F, Rouanet P, Barjot C, Janmot C, Vigneron P, d'Albis A. Expression of myosin isoforms in denervated, cross‐reinnervated, and electrically stimulated rabbit muscles. Eur J Biochem 236: 539‐547, 1996.
 22.Baehr LM, Furlow JD, Bodine SC. Muscle sparing in muscle RING finger 1 null mice: Response to synthetic glucocorticoids. J Physiol 589: 4759‐4776, 2011.
 23.Baker JH, Poindextor CE. Muscle regeneration following segmental necrosis in tenotomized muscle fibers. Muscle & nerve 14: 348‐357, 1991.
 24.Bakkar N, Ladner K, Canan BD, Liyanarachchi S, Bal NC, Pant M, Periasamy M, Li Q, Janssen PM, Guttridge DC. IKKalpha and alternative NF‐kappaB regulate PGC‐1beta to promote oxidative muscle metabolism. J Cell Biol 196: 497‐511, 2012.
 25.Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, Pant M, Rowland LA, Bombardier E, Goonasekera SA, Tupling AR, Molkentin JD, Periasamy M. Sarcolipin is a newly identified regulator of muscle‐based thermogenesis in mammals. Nature Medicine 18: 1575‐1579, 2012.
 26.Baldwin K, Herrick R, McCue S. Substrate oxidation capacity in rodent skeletal muscle: Effects of exposure to zero gravity. J Appl Physiol 75: 2466‐2470, 1993.
 27.Baldwin KM, Cheadle WG, Martinez OM, Cooke DA. Effect of functional overload on enzyme levels in different types of skeletal muscle. J Appl Physiol 42: 312‐317, 1977.
 28.Baldwin KM, Haddad F. Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol 90: 345‐357, 2001.
 29.Balon T, Nadler J. Nitric oxide release is present from incubated skeletal muscle preparations. J Appl Physiol 77: 2519‐2521, 1994.
 30.Barbieri E, Sestili P. Reactive oxygen species in skeletal muscle signaling. J Signal Transduct 2012: 982794, 2012.
 31.Barclay CG, Constable JK, Gibbs CL. Energetics of fast‐ and slow‐twitch muscles of the mouse. J Physiol 472: 61‐80, 1993.
 32.Bartsch P, Saltin B. General introduction to altitude adaptation and mountain sickness. Scand J Med Sci Sports 18(Suppl 1): 1‐10, 2008.
 33.Bassel‐Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem 75: 19‐37, 2006.
 34.Baylor S, Hollingworth S. Intracellular calcium movements during excitation‐contraction coupling in mammalian slow‐twitch and fast‐twitch muscle fibers. J Gen Physiol 139: 261‐272, 2012.
 35.Baylor SM, Hollingworth S. Sarcoplasmic reticulum calcium release compared in slow‐twitch and fast‐twitch fibres of mouse muscle. J Physiol 551: 125‐138, 2003.
 36.Bellinger AM, Reiken S, Dura M, Murphy PW, Deng SX, Landry DW, Nieman D, Lehnart SE, Samaru M, LaCampagne A, Marks AR. Remodeling of ryanodine receptor complex causes “leaky” channels: A molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci U S A 105: 2198‐2202, 2008.
 37.Benson D, Foley‐Nelson T, Chance W, Zhang F, James J, and Fischer J. Decreased myofibrillar protein breakdown following treatment with clenbuterol. J Surg Res 50: 1‐5, 1991.
 38.Bentzinger CF, Romanino K, Cloetta D, Lin S, Mascarenhas JB, Oliveri F, Xia J, Casanova E, Costa CF, Brink M, Zorzato F, Hall MN, Ruegg MA. Skeletal muscle‐specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab 8: 411‐424, 2008.
 39.Berg DK, Kelly RB, Sargent PB, Williamson P, Hall ZW. Binding of ‐bungarotoxin to acetylcholine receptors in mammalian muscle (snake venom‐denervated muscle‐neonatal muscle‐rat diaphragm‐SDS‐polyacrylamide gel electrophoresis). Proc Natl Acad Sci U S A 69: 147‐151, 1972.
 40.Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 70: 1882‐1885, 1991.
 41.Berg HE, Larsson L, Tesch PA. Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol 82: 182‐188, 1997.
 42.Bezakova G, Lømo T. Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers. J Cell Biol 153 1453‐1463, 2001.
 43.Bhasin S, Woodhouse L, Casaburi R, Singh A, Bhasin D, Berman N, Dzekov J, Bross R, Phillips J, Sinha‐Hikim I, Shen R, Storer T. Testosterone dose–response relationships in healthy young men. Am J Physiol Endocrinol Metab 281: E1172‐E1181, 2001.
 44.Biering‐Sørensen B, Kristensen I, Kjaer M, Biering‐Sørensen F. Muscle after spinal cord injury. Muscle Nerve 40: 499‐519, 2009.
 45.Bisht B, Goel HL, Dey CS. Focal adhesion kinase regulates insulin resistance in skeletal muscle. Diabetologia 50: 1058‐1069, 2007.
 46.Bisht B, Srinivasan K, Dey CS. In vivo inhibition of focal adhesion kinase causes insulin resistance. J Physiol 586: 3825‐3837, 2008.
 47.Bizeau M, Willis W, Hazel J. Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria. J Appl Physiol 85: 1279‐1284, 1998.
 48.Blaauw B, Agatea L, Toniolo L, Canato M, Quarta M, Dyar KA, Danieli‐Betto D, Betto R, Schiaffino S, Reggiani C. Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy. J Appl Physiol 108: 105‐111, 2010.
 49.Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, Abraham R, Sandri M, Schiaffino S, Reggiani C. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J 23: 3896‐3905, 2009.
 50.Blaauw B, Del Piccolo P, Rodriguez L, Hernandez Gonzalez VH, Agatea L, Solagna F, Mammano F, Pozzan T, Schiaffino S. No evidence for inositol 1,4,5‐trisphosphate‐dependent Ca2 +release in isolated fibers of adult mouse skeletal muscle. J Gen Physiol 140: 235‐241, 2012.
 51.Blaauw B, Mammucari C, Toniolo L, Agatea L, Abraham R, Sandri M, Reggiani C, Schiaffino S. Akt activation prevents the force drop induced by eccentric contractions in dystrophin‐deficient skeletal muscle. Hum Mol Genet 17: 3686‐3696, 2008.
 52.Blackshear PJ, Stumpo DJ, Carballo E, Lawrence JC, Jr. Disruption of the gene encoding the mitogen‐regulated translational modulator PHAS‐I in mice. J Biol Chem 272: 31510‐31514, 1997.
 53.Blattler SM, Cunningham JT, Verdeguer F, Chim H, Haas W, Liu H, Romanino K, Ruegg MA, Gygi SP, Shi Y, Puigserver P. Yin Yang 1 deficiency in skeletal muscle protects against rapamycin‐induced diabetic‐like symptoms through activation of insulin/IGF signaling. Cell metabolism 15: 505‐517, 2012.
 54.Blattler SM, Verdeguer F, Liesa M, Cunningham JT, Vogel RO, Chim H, Liu H, Romanino K, Shirihai OS, Vazquez F, Ruegg MA, Shi Y, Puigserver P. Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle. Mol Cell Biol 32: 3333‐3346, 2012.
 55.Blei ML, Conley KE, Kushmerick MJ. Separate measures of ATP utilization and recovery in human skeletal muscle. J Physiol 465: 203‐222, 1993.
 56.Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294: 1704‐1708, 2001.
 57.Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3: 1014‐1019, 2001.
 58.Bonen A. PGC‐1alpha‐induced improvements in skeletal muscle metabolism and insulin sensitivity. Appl Physiol Nutr Metab 34: 307‐314, 2009.
 59.Booth FW. Effect of limb immobilization on skeletal muscle. J Appl Physiol 52: 1113‐1118, 1982.
 60.Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: Perspectives of various models. Physiol Rev 71: 541‐585, 1991.
 61.Bottinelli R, Betto R, Schiaffino S, Reggiani C. Maximum shortening velocity and coexistence of myosin heavy chain isoforms in single skinned fast fibres of rat skeletal muscle. J Muscle Res Cell Motil 15: 413‐419, 1994.
 62.Bottinelli R, Canepari M, Reggiani C, Stienen GJ. Myofibrillar ATPase activity during isometric contraction and isomyosin composition in rat single skinned muscle fibres. J Physiol 481: 663‐675, 1994.
 63.Boudriau S, Cote CH, Vincent M, Houle P, Tremblay RR, Rogers PA. Remodeling of the cytoskeletal lattice in denervated skeletal muscle. Muscle Nerve 19: 1383‐1390, 1996.
 64.Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134: 707‐716, 1973.
 65.Brancaccio M, Fratta L, Notte A, Hirsch E, Poulet R, Guazzone S, De Acetis M, Vecchione C, Marino G, Altruda F, Silengo L, Tarone G, Lembo G. Melusin, a muscle‐specific integrin beta1‐interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nat Med 9: 68‐75, 2003.
 66.Brancaccio M, Guazzone S, Menini N, Sibona E, Hirsch E, De Andrea M, Rocchi M, Altruda F, Tarone G, Silengo L. Melusin is a new muscle‐specific interactor for beta(1) integrin cytoplasmic domain. J Biol Chem 274: 29282‐29288, 1999.
 67.Brenner B, Eisenberg E. Rate of force generation in muscle: Correlation with actomyosin ATPase activity in solution. Proc Natl Acad Sci U S A 83: 3542‐3546, 1986.
 68.Brocca L, Cannavino J, Coletto L, Biolo G, Sandri M, Bottinelli R, Pellegrino MA. The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. J Physiol 590: 5211‐5230, 2012.
 69.Brocca L, Pellegrino MA, Desaphy JF, Pierno S, Camerino DC, Bottinelli R. Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb‐unloaded mice. Exp Physiol 95: 331‐350, 2010.
 70.Brodal P, Ingjer F, Hermansen L. Capillary supply of skeletal muscle fibers in untrained and endurance‐trained men. Am J Physiol 232: 705‐712, 1977.
 71.Brown G, Bulbring E, Burns B. The action of adrenaline on mammalian skeletal muscle. J Physiol 107: 115‐128, 1948.
 72.Brown M, Cotter M, Hudlická O, Vrbová G. The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pflugers Arch 361: 241‐250, 1976.
 73.Brownson C, Little P, Jarvis J, Salmons S. Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation. Muscle Nerve 15: 694‐700, 1992.
 74.Bruusgaard JC, Egner IM, Larsen TK, Dupre‐Aucouturier S, Desplanches D, Gundersen K. No change in myonuclear number during muscle unloading and reloading. J Appl Physiol 113: 290‐296, 2012.
 75.Bruusgaard JC, Gundersen K. In vivo time‐lapse microscopy reveals no loss of murine myonuclei during weeks of muscle atrophy. J Clin Invest 118: 1450‐1457, 2008.
 76.Bruusgaard JC, Johansen IB, Egner IM, Rana ZA, Gundersen K. Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proc Natl Acad Sci U S A 107: 15111‐15116, 2010.
 77.Buller AJ, Eccles JC, Eccles RM. Interactions between motoneurons and muscles in respect of the characteristic speeds of their responses. J Physiol 150: 417‐439, 1960.
 78.Buller AJ, Kean CJ, Ranatunga KW. The force‐velocity characteristics of cat fast and slow‐twitch skeletal muscle following cross‐innervation. J Physiol 213: 66P‐67P, 1971.
 79.Buller AJ, Lewis DM. Some Observations on the Effects of Tenotomy in the Rabbit. J Physiol 178: 326‐342, 1965.
 80.Buller AJ, Mommaerts WF, Seraydarian K. Neural control of myofibrillar ATPase activity in rat skeletal muscle. Nat New Biol 233: 31‐32, 1971.
 81.Burd NA, Holwerda AM, Selby KC, West DW, Staples AW, Cain NE, Cashaback JG, Potvin JR, Baker SK, Phillips SM. Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men. J Physiol 588: 3119‐3130, 2010.
 82.Burke RE, Levine DN, Zajac FE. Mammalian motor units: Physiological‐histochemical correlation in three types in cat gastrocnemius. Science 174: 709‐712, 1971.
 83.Burridge K, Chrzanowska‐Wodnicka M. Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12: 463‐518, 1996.
 84.Cai D, Frantz JD, Tawa NE, Jr., Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE. IKKbeta/NF‐kappaB activation causes severe muscle wasting in mice. Cell 119: 285‐298, 2004.
 85.Caiozzo V, Haddad F, Baker M, Herrick R, Prietto N, Baldwin K. Microgravity‐induced transformations of myosin isoforms and contractile properties of skeletal muscle. J Appl Physiol 81: 123‐132, 1996.
 86.Caiozzo VJ, Baker MJ, Baldwin KM. Modulation of myosin isoform expression by mechanical loading: Role of stimulation frequency. J Appl Physiol 82: 211‐218, 1997.
 87.Caiozzo VJ, Baker MJ, Baldwin KM. Novel transitions in MHC isoforms: Separate and combined effects of thyroid hormone and mechanical unloading. J Appl Physiol 85: 2237‐2248, 1998.
 88.Caiozzo VJ, Haddad F, Baker M, McCue S, Baldwin KM. MHC polymorphism in rodent plantaris muscle: Effects of mechanical overload and hypothyroidism. Am J Physiol Cell Physiol 278: C709‐C717, 2000.
 89.Caiozzo VJ, Haddad F, Baker MJ, Baldwin KM. Influence of mechanical loading on myosin heavy‐chain protein and mRNA isoform expression. J Appl Physiol 80: 1503‐1512, 1996.
 90.Cairns S, Dulhunty A. The effects of beta‐adrenoceptor activation on contraction in isolated fast‐ and slow‐twitch skeletal muscle fibres of the rat. Br J Pharmacol 110: 1133‐1141, 1993.
 91.Calderon JC, Bolanos P, Caputo C. Myosin heavy chain isoform composition and Ca(2+) transients in fibres from enzymatically dissociated murine soleus and extensor digitorum longus muscles. J Physiol 588: 267‐279, 2010.
 92.Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J, Willis MS, Selzman CH, Wang DZ. MicroRNA‐208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 119: 2772‐2786, 2009.
 93.Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM. Muscle‐specific expression of PPARgamma coactivator‐1alpha improves exercise performance and increases peak oxygen uptake. J Appl Physiol 104: 1304‐1312, 2008.
 94.Canto C, Gerhart‐Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458: 1056‐1060, 2009.
 95.Carling D, Mayer FV, Sanders MJ, Gamblin SJ. AMP‐activated protein kinase: Nature's energy sensor. Nature Chem Biol 7: 512‐518, 2011.
 96.Carlson LD. Cardiovascular studies during and following simulation and weightlessness. Life Sci Space Res 5: 51‐54, 1967.
 97.Carroll T, Abernethy P, Logan P, Barber M, McEniery M. Resistance training frequency: Strength and myosin heavy chain responses to two and three bouts per week. Eur J Appl Physiol 78: 270‐275, 1998.
 98.Castillo A, Nowak R, Littlefield KP, Fowler VM, Littlefield RS. A nebulin ruler does not dictate thin filament lengths. Biophys J 96: 1856‐1865, 2009.
 99.Chakkalakal JV, Nishimune H, Ruas JL, Spiegelman BM, Sanes JR. Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons. Development 137: 3489‐3499, 2010.
 100.Chan A, Edgerton V, Goslow GJ, Kurata H, Rasmussen S, Spector S. Histochemical and physiological properties of cat motor units after self‐and cross‐reinnervation. J Physiol 332: 343‐361, 1982.
 101.Chemello F, Bean C, Cancellara P, Laveder P, Reggiani C, Lanfranchi G. Microgenomic analysis in skeletal muscle: Expression signatures of individual fast and slow myofibers. PLoS One 6: e16807, 2011.
 102.Cheung TH, Quach NL, Charville GW, Liu L, Park L, Edalati A, Yoo B, Hoang P, Rando TA. Maintenance of muscle stem‐cell quiescence by microRNA‐489. Nature 482: 524‐528, 2012.
 103.Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel‐Duby R, Williams RS. A calcineurin‐dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev 12: 2499‐2509, 1998.
 104.Choi CS, Befroy DE, Codella R, Kim S, Reznick RM, Hwang YJ, Liu ZX, Lee HY, Distefano A, Samuel VT, Zhang D, Cline GW, Handschin C, Lin J, Petersen KF, Spiegelman BM, Shulman GI. Paradoxical effects of increased expression of PGC‐1alpha on muscle mitochondrial function and insulin‐stimulated muscle glucose metabolism. Proc Natl Acad Sci U S A 105: 19926‐19931, 2008.
 105.Chopard A, Hillock S, Jasmin BJ. Molecular events and signalling pathways involved in skeletal muscle disuse‐induced atrophy and the impact of countermeasures. J Cell Mol Med 13: 3032‐3050, 2009.
 106.Churchward‐Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: Effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol 590: 2751‐2765, 2012.
 107.Clark SJ, Harrison J, Frommer M. CpNpG methylation in mammalian cells. Nat Genet 10: 20‐27, 1995.
 108.Clarke BA, Drujan D, Willis MS, Murphy LO, Corpina RA, Burova E, Rakhilin SV, Stitt TN, Patterson C, Latres E, Glass DJ. The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone‐treated skeletal muscle. Cell Metab 6: 376‐385, 2007.
 109.Clarkson PM, Devaney JM, Gordish‐Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Hoffman EP. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol 99: 154‐163, 2005.
 110.Clement K, Viguerie N, Diehn M, Alizadeh A, Barbe P, Thalamas C, Storey J, Brown P, Barsh G, Langin D. In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res 12: 281‐291, 2002.
 111.Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, Hawley JA. Early signaling responses to divergent exercise stimuli in skeletal muscle from well‐trained humans. FASEB J 20: 190‐192, 2006.
 112.Cohen S, Brault JJ, Gygi SP, Glass DJ, Valenzuela DM, Gartner C, Latres E, Goldberg AL. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1‐dependent ubiquitylation. J Cell Biol 185: 1083‐1095, 2009.
 113.Cohen S, Zhai B, Gygi SP, Goldberg AL. Ubiquitylation by Trim32 causes coupled loss of desmin, Z‐bands, and thin filaments in muscle atrophy. J Cell Biol 198: 575‐589, 2012.
 114.Coker RH, Wolfe RR. Bedrest and sarcopenia. Curr Opin Clin Nutr Metab Care 15: 7‐11, 2012.
 115.Costill DL, Daniels J, Evans W, Fink W, Krahenbuhl G, Saltin B. Skeletal muscle enzymes and fiber composition in male and female track athletes. J Appl Physiol 40: 149‐154, 1976.
 116.Couillard A, Prefaut C. From muscle disuse to myopathy in COPD: Potential contribution of oxidative stress. Eur Respir J 26: 703‐719, 2005.
 117.Crabtree GR, Schreiber SL. SnapShot: Ca2+‐calcineurin‐NFAT signaling. Cell 138: 210‐211, 2009.
 118.Crameri R, Langberg H, Magnusson P, Jensen C, Schroder H, Olesen J, Suetta C, Teisner B, Kjaer M. Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise. J Physiol 558: 333‐340, 2004.
 119.Crow MT, Kushmerick MJ. Chemical energetics of slow‐ and fast‐twitch muscles of the mouse. J Gen Physiol 79: 147‐166, 1982.
 120.Csibi A, Cornille K, Leibovitch MP, Poupon A, Tintignac LA, Sanchez AM, Leibovitch SA. The translation regulatory subunit eIF3f controls the kinase‐dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS One 5: e8994, 2010.
 121.Csibi A, Leibovitch MP, Cornille K, Tintignac LA, Leibovitch SA. MAFbx/Atrogin‐1 controls the activity of the initiation factor eIF3‐f in skeletal muscle atrophy by targeting multiple C‐terminal lysines. J Biol Chem 284: 4413‐4421, 2009.
 122.Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1‐PGC‐1alpha transcriptional complex. Nature 450: 736‐740, 2007.
 123.D'Antona G, Lanfranconi F, Pellegrino MA, Brocca L, Adami R, Rossi R, Moro G, Miotti D, Canepari M, Bottinelli R. Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders. J Physiol 570: 611‐627, 2006.
 124.Dapp C, Schmutz S, Hoppeler H, Fluck M. Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle. Physiol Genomics 20: 97‐107, 2004.
 125.Davies K, Quintanilha A, Brooks G, Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107: 1198‐1205, 1982. Boer MD, Maganaris CN, Seynnes OR, Rennie MJ, Narici MV. Time course of muscular, neural and tendinous adaptations to 23 day unilateral lower‐limb suspension in young men. J Physiol 583: 1079‐1091, 2007. Boer MD, Seynnes OR, di Prampero PE, Pisot R, Mekjavic IB, Biolo G, Narici MV. Effect of 5 weeks horizontal bed rest on human muscle thickness and architecture of weight bearing and non‐weight bearing muscles. Eur J Appl Physiol 104: 401‐407, 2008.
 128.Deavers DR, Musacchia XJ, Meininger GA. Model for antiorthostatic hypokinesia: Head‐down tilt effects on water and salt excretion. J Appl Physiol 49: 576‐582, 1980.
 129.Decramer M, de Bock V, Dom R. Functional and histologic picture of steroidinduced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 153: 1958‐1964, 1996.
 130.Dekhuijzen P, Gayan‐Ramirez G, Bisschop A, de Bock V, Dom R, Decramer M. Corticosteroid treatment and nutritional deprivationcause a different pattern of atrophy in rat diaphragm. J Appl Physiol 78: 629‐637, 1995.
 131.DeNardi C, Ausoni S, Moretti P, Gorza L, Velleca M, Buckingham M, Schiaffino S. Type 2X‐myosin heavy chain is coded by a muscle fiber type‐specific and developmentally regulated gene. J Cell Biol 123: 823‐835, 1993.
 132.Desaphy JF, Pierno S, Liantonio A, Giannuzzi V, Digennaro C, Dinardo MM, Camerino GM, Ricciuti P, Brocca L, Pellegrino MA, Bottinelli R, Camerino DC. Antioxidant treatment of hindlimb‐unloaded mouse counteracts fiber type transition but not atrophy of disused muscles. Pharmacol Res 61: 553‐563, 2010.
 133.Deshmukh AS, Treebak JT, Long YC, Viollet B, Wojtaszewski JF, Zierath JR. Role of adenosine 5'‐monophosphate‐activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling. Mol Endocrinol 22: 1105‐1112, 2008.
 134.Desplanches D, Mayet M, Ilyina‐Kakueva E, Frutoso J, Flandrois R. Structural and metabolic properties of rat muscle exposed to weightlessness aboard Cosmos 1887. Eur J Appl Physiol Occup Physiol 63: 288‐292, 1991.
 135.Di Prampero PE, Narici MV. Muscles in microgravity: From fibers to human motion. J Biomech 36: 403‐412, 2003.
 136.DiPasquale DM, Cheng M, Billich W, Huang SA, van Rooijen N, Hornberger TA, Koh TJ. Urokinase‐type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice. Am J Physiol Cell Physiol 293: C1278‐C1285, 2007.
 137.Dolmetsch RE, Xu K, Lewis RS. Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392: 933‐936, 1998.
 138.Doria C, Toniolo L, Verratti V, Cancellara P, Pietrangelo T, Marconi V, Paoli A, Pogliaghi S, Fano G, Reggiani C, Capelli C. Improved VO2 uptake kinetics and shift in muscle fiber type in high‐altitude trekkers. J Appl Physiol 111: 1597‐1605, 2011.
 139.Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, Kozma SC, Thomas G, Sonenberg N. mTORC1‐mediated cell proliferation, but not cell growth, controlled by the 4E‐BPs. Science 328: 1172‐1176, 2010.
 140.Drenning JA, Lira VA, Simmons CG, Soltow QA, Sellman JE, Criswell DS. Nitric oxide facilitates NFAT‐dependent transcription in mouse myotubes. Am J Physiol Cell Physiol 294: C1088‐C1095, 2008.
 141.Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB. Leucine‐enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294: E392‐E400, 2008.
 142.Droppert P. A review of muscle atrophy in microgravity and during prolonged bed rest. J Br Interplanet Soc 46: 83‐86, 1993.
 143.Dumont N, Bouchard P, Frenette J. Neutrophil‐induced skeletal muscle damage: A calculated and controlled response following hindlimb unloading and reloading. Am J Physiol Regul Integr Comp Physiol 295: R1831‐R1838, 2008.
 144.Eddy SF, Storey KB. Differential expression of Akt, PPARgamma, and PGC‐1 during hibernation in bats. Biochem Cell Biol 81: 269‐274, 2003.
 145.Edgerton V, Roy R. Neuromuscular adaptations to actual and simulated spaceflight. In: Handbook of Physiology: Environmental physiology, Edited by MJ Fregley and CM Blatteis; Published by American Physiological Society, Bethesda (MD), pp. 721‐763, 1996.
 146.Edgerton VR, Goslow GE, Jr., Rasmussen SA, Spector SA. Is resistance of a muscle to fatigue controlled by its motoneurones? Nature 285: 589‐590, 1980.
 147.Eisele PS, Salatino S, Sobek J, Hottiger MO, Handschin C. The peroxisome proliferator‐activated receptor gamma coactivator 1alpha/beta (PGC‐1) coactivators repress the transcriptional activity of NF‐kappaB in skeletal muscle cells. J Biol Chem 288: 2246‐2260, 2013.
 148.Eken T, Gundersen K. Electrical stimulation resembling normal motorunitactivity: Effects on denervated fast and slow rat muscles. J Physiol 402: 651‐669, 1988.
 149.Eliasson J, Elfegoun T, Nilsson J, Kohnke R, Ekblom B, Blomstrand E. Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol Endocrinol Metab 291: E1197‐E1205, 2006.
 150.Engel WK, Brooke MH, Nelson PG. Histochemical studies of denervated or tenotomized cat muscle: Illustrating difficulties in relating experimental animal conditions to human neuromuscular diseases. Ann N Y Acad Sci 138: 160‐185, 1966.
 151.Eriksson A, Kadi F, Malm C, Thornell LE. Skeletal muscle morphology in power‐lifters with and without anabolic steroids. Histochem Cell Biol 124: 167‐175, 2005.
 152.Ervasti JM. Costameres: The Achilles' heel of Herculean muscle. J Biol Chem 278: 13591‐13594, 2003.
 153.Estrada M, Espinosa A, Müller M, Jaimovich E. Testosterone stimulates intracellular calcium release and mitogen‐activated protein kinases via a G protein‐coupled receptor in skeletal muscle cells. Endocrinology 144: 3586‐3597, 2003.
 154.Fenton TR, and Gout IT. Functions and regulation of the 70kDa ribosomal S6 kinases. Intern J Biochem & Cell Biol 43: 47‐59, 2011.
 155.Ferrando A, Tipton K, Doyle D, Phillips S, Cortiella J, Wolfe R. Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol ‐ Endocrinol and Metab 275: E864‐E871, 1998.
 156.Ferretti G, Berg HE, Minetti AE, Moia C, Rampichini S, Narici MV. Maximal instantaneous muscular power after prolonged bed rest in humans. J Appl Physiol 90: 431‐435, 2001.
 157.Fitts R, Riley D, Widrick J. Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol 204: 3201‐3208, 2001.
 158.Fitts RH, Trappe SW, Costill DL, Gallagher PM, Creer AC, Colloton PA, Peters JR, Romatowski JG, Bain JL, Riley DA. Prolonged space flight‐induced alterations in the structure and function of human skeletal muscle fibres. J Physiol 588: 3567‐3592, 2010.
 159.Fladby T, Jansen J. Development of homogeneous fast and slow motor units in the neonatal mouse soleus muscle. Development 109: 723‐732, 1990.
 160.Fluck M, Carson JA, Gordon SE, Ziemiecki A, Booth FW. Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle. Am J Physiol 277: C152‐C162, 1999.
 161.Fluck M, Hoppeler H. Molecular basis of skeletal muscle plasticity–from gene to form and function. Rev Physiol Biochem Pharmacol 146: 159‐216, 2003.
 162.Foehring RC, Sypert GW, Munson JB. Motor‐unit properties following cross‐reinnervation of cat lateral gastrocnemius and soleus muscles with medial gastrocnemius nerve. I. Influence of motoneurons on muscle. J Neurophysiol 57: 1210‐1226, 1987a.
 163.Foehring RC, Sypert GW, Munson JB. Motor‐unit properties following cross‐reinnervation of cat lateral gastrocnemius and soleus muscles with medial gastrocnemius nerve. II. Influence of muscle on motoneurons. J Neurophysiol 57: 1227‐1245, 1987b.
 164.Fournier M, Roy RR, Perham H, Simard CP, Edgerton VR. Is limb immobilization a model of muscle disuse? Exp Neurol 80: 147‐156, 1983.
 165.Franssen FM, Wouters EF, Schols AM. The contribution of starvation, deconditioning and ageing to the observed alterations in peripheral skeletal muscle in chronic organ diseases. Clin Nutr 21: 1‐14, 2002.
 166.Frey N, Olson EN. Cardiac hypertrophy: The good, the bad, and the ugly. Annu Rev Physiol 65: 45‐79, 2003.
 167.Frontera WR, Zayas AR, Rodriguez N. Aging of human muscle: Understanding sarcopenia at the single muscle cell level. Phys Med Rehabil Clin N Am 23: 201‐207, 2012.
 168.Fujita S, Rasmussen BB, Cadenas JG, Drummond MJ, Glynn EL, Sattler FR, Volpi E. Aerobic exercise overcomes the age‐related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes 56: 1615‐1622, 2007.
 169.Gallagher P, Trappe S, Harber M, Creer A, Mazzetti S, Trappe T, Alkner B, Tesch P. Effects of 84‐days of bedrest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles. Acta Physiol Scand 185: 61‐69, 2005.
 170.Gayraud‐Morel B, Chretien F, Flamant P, Gomes D, Zammit PS, Tajbakhsh S. A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Dev Biol 312: 13‐28, 2007.
 171.Geiger PC, Cody M, Sieck G. Force‐calcium relationship depends on myosin heavy chain and troponin isoforms in rat diaphragm muscle fibers. J Appl Physiol 87: 1894‐1900, 1999.
 172.Gerhart‐Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1alpha. EMBO J 26: 1913‐1923, 2007.
 173.Giannoulis MG, Sonksen PH, Umpleby M, Breen L, Pentecost C, Whyte M, McMillan C, Bradley C, Martin FC. The effects of growth hormone and/or testosterone in healthy elderly men: A randomized controlled trial. J Clin Endocrinol Metabol 91: 477‐484, 2006.
 174.Gillespie MJ, Gordon T, Murphy PR. Motor units and histochemistry in rat lateral gastrocnemius and soleus muscles: Evidence for dissociation of physiological and histochemical properties after reinnervation. J Neurophysiol 57: 921‐937, 1987.
 175.Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 5: 87‐90, 2003.
 176.Gold E, and Risbridger G. Activins and activin antagonists in the prostate and prostate cancer. Mol Cell Endocrinol 359: 107‐112, 2012.
 177.Goldberg A, Tischler M, DeMartino G, and Griffin G. Hormonal regulation of protein degradation and synthesis in skeletal muscle. Federation Proceedings 39: 31‐36, 1980.
 178.Goldspink DF. The influence of immobilization and stretch on protein turnover of rat skeletal muscle. J Physiol 264: 267‐282, 1977.
 179.Goldspink DF. The influence of passive stretch on the growth and protein turnover of the denervated extensor digitorum longus muscle. Biochem J 174: 595‐602, 1978.
 180.Goldspink G. Mechanical signals, IGF‐I gene splicing, and muscle adaptation. Physiology (Bethesda) 20: 232‐238, 2005.
 181.Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin‐1, a muscle‐specific F‐box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98: 14440‐14445, 2001.
 182.Gomez‐Cabrera MC, Borras C, Pallardo FV, Sastre J, Ji LL, Vina J. Decreasing xanthine oxidase‐mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol 567: 113‐120, 2005.
 183.Goodman CA, Miu MH, Frey JW, Mabrey DM, Lincoln HC, Ge Y, Chen J, Hornberger TA. A phosphatidylinositol 3‐kinase/protein kinase B‐independent activation of mammalian target of rapamycin signaling is sufficient to induce skeletal muscle hypertrophy. Mol Biol Cell 21: 3258‐3268, 2010.
 184.Goonasekera SA, Lam CK, Millay DP, Sargent MA, Hajjar RJ, Kranias EG, Molkentin JD. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J Clin Invest 121: 1044‐1052, 2011.
 185.Gordon A, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev 80: 853‐924, 2000.
 186.Granzier HL, Labeit S. The giant muscle protein titin is an adjustable molecular spring. Exerc Sport Sci Rev 34: 50‐53, 2006.
 187.Grater F, Shen J, Jiang H, Gautel M, Grubmuller H. Mechanically induced titin kinase activation studied by force‐probe molecular dynamics simulations. Biophys J 88: 790‐804, 2005.
 188.Greising SM, Gransee HM, Mantilla CB, Sieck GC. Systems biology of skeletal muscle: Fiber type as an organizing principle. Wiley Interdiscip Rev Syst Biol Med 4: 457‐473, 2012.
 189.Grimby G, Broberg C, Krotkiewska I, Krotkiewski M. Muscle fiber composition in patients with traumatic cord lesion. Scand J Rehabil Med 8: 37‐42, 1976.
 190.Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, Blaauw B, Urciuolo A, Tiepolo T, Merlini L, Maraldi NM, Bernardi P, Sandri M, Bonaldo P. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nature Medicine 16: 1313‐1320, 2010.
 191.Grumati P, Coletto L, Sandri M, Bonaldo P. Autophagy induction rescues muscular dystrophy. Autophagy 7: 426‐428, 2011.
 192.Gulati P, Gaspers LD, Dann SG, Joaquin M, Nobukuni T, Natt F, Kozma SC, Thomas AP, Thomas G. Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab 7: 456‐465, 2008.
 193.Gundersen K. Excitation‐transcription coupling in skeletal muscle: The molecular pathways of exercise. Biol Rev Camb Philos Soc 86: 564‐600, 2011.
 194.Gundersen K, Leberer E, Lømo T, Pette D, Staron R. Fibre types, calcium‐sequestering proteins and metabolic enzymes in denervated and chronically stimulated muscles of the rat. J Physiol 398: 177‐189, 1988.
 195.Gustafsson T, Osterlund T, Flanagan JN, von Walden F, Trappe TA, Linnehan RM, Tesch PA. Effects of 3 days unloading on molecular regulators of muscle size in humans. J Appl Physiol 109: 721‐727, 2010.
 196.Gutman E, Zelena J. Morphological changes in the denervated muscle. The Denervated Muscle, Publishing House of Czeckoslovack Academy of Sciences, Prague, 57‐102, 1962.
 197.Gutmann E, Hanzlíková V, Lojda Z. Effect of androgens on histochemicalfibre type. Differentiation in the temporal muscle of the guinea pig. Histochemie 24: 287‐291, 1970.
 198.Gutmann E, Schiaffino S, Hanzlikova V. Mechanism of compensatory hypertrophy in skeletal muscle of the rat. Exp Neurol 31: 451‐464, 1971.
 199.Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30: 214‐226, 2008.
 200.Hackney KJ, Ploutz‐Snyder LL. Unilateral lower limb suspension: Integrative physiological knowledge from the past 20 years (1991‐2011). Eur J Appl Physiol 112: 9‐22, 2012.
 201.Hagiwara N, Ma B, Ly A. Slow and fast fiber isoform gene expression is systematically altered in skeletal muscle of the Sox6 mutant, p100H. Dev Dyn 234: 301‐311, 2005.
 202.Hämäläinen N, Pette D. Slow‐to‐fast transitions in myosin expression of rat soleus muscle by phasic high‐frequency stimulation. FEBS Lett 16: 220‐222, 1996.
 203.Hamburg NM, McMackin CJ, Huang AL, Shenouda SM, Widlansky ME, Schulz E, Gokce N, Ruderman NB, Keaney JF, Jr., Vita JA. Physical inactivity rapidly induces insulin resistance and microvascular dysfunction in healthy volunteers. Arterioscler Thromb Vasc Biol 27: 2650‐2656, 2007.
 204.Handschin C, Chin S, Li P, Liu F, Maratos‐Flier E, Lebrasseur NK, Yan Z, Spiegelman BM. Skeletal muscle fiber‐type switching, exercise intolerance, and myopathy in PGC‐1alpha muscle‐specific knock‐out animals. J Biol Chem 282: 30014‐30021, 2007.
 205.Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM. Abnormal glucose homeostasis in skeletal muscle‐specific PGC‐1alpha knockout mice reveals skeletal muscle‐pancreatic beta cell crosstalk. J Clin Invest 117: 3463‐3474, 2007.
 206.Hanzlíková V, Schiaffino S, Settembrini P. Histochemical fiber types characteristics in the normal and the persistent levatorani muscle of the rat. Histochemie 22: 45‐50, 1970.
 207.Harlow HJ, Lohuis T, Beck TD, Iaizzo PA. Muscle strength in overwintering bears. Nature 409: 997, 2001.
 208.Harridge SD. Plasticity of human skeletal muscle: Gene expression to in vivo function. Exp Physiol 92: 783‐797, 2007.
 209.Harrison BC, Allen DL, Girten B, Stodieck LS, Kostenuik PJ, Bateman TA, Morony S, Lacey D, Leinwand LA. Skeletal muscle adaptations to microgravity exposure in the mouse. J Appl Physiol 95: 2462‐2470, 2003.
 210.Harvey C, Williams G. Mechanism of thyroid hormone action. Thyroid 12: 441‐446, 2002.
 211.Hasselgren PO. Glucocorticoids and muscle catabolism. Curr Op Clin Nut and Met Care 2: 201‐205, 1999.
 212.Hauschka SD. The embryonic origin of muscle. Myology 3‐73, 1994.
 213.Hayes A, Williams D. Long‐term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin‐deficient mdx mice. Clin Exp Pharmacol Physiol 21: 757‐765, 1994.
 214.He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel‐Duby R, Scherer PE, Levine B. Exercise‐induced BCL2‐regulated autophagy is required for muscle glucose homeostasis. Nature 481: 511‐515, 2012.
 215.Heineke J, Ruetten H, Willenbockel C, Gross SC, Naguib M, Schaefer A, Kempf T, Hilfiker‐Kleiner D, Caroni P, Kraft T, Kaiser RA, Molkentin JD, Drexler H, Wollert KC. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein‐calcineurin signaling at the sarcomeric Z‐disc. Proc Natl Acad Sci U S A 102: 1655‐1660, 2005.
 216.Hennig R, Lomo T. Firing patterns of motor units in normal rats. Nature 314: 164‐166, 1985.
 217.Henriksson J, Chi M, Hintz C, Young D, Kaiser K, Salmons S, Lowry O. Chronic stimulation of mammalian muscle: Changes in enzymes of six metabolic pathways. Am J Physiol Cell Physiol 251: C614‐C632, 1986.
 218.Hidalgo C, Granzier H. Tuning the molecular giant titin through phosphorylation: Role in health and disease. Trends Cardiovasc Med 23: 165‐171, 2013.
 219.Hochachka PW, Stanley C, Merkt J, SumarKalinowski J. Metabolic meaning of elevated levels of oxidative enzymes in high altitude adapted animals: An interpretive hypothesis. Respir Physiol 52: 303‐313, 1983.
 220.Hofmann S, Pette D. Low‐frequency stimulation of rat fast‐twitch muscle enhances the expression of hexokinase II and both the translocation and expression of glucose transporter 4 (GLUT‐4). Eur J Biochem 219: 307‐315, 1994.
 221.Hoh JF. Neural regulation of mammalian fast and slow muscle myosins: An electrophoretic analysis. Biochemistry 14: 742‐747, 1975.
 222.Hoh JF, Hughes S. Myogenic and neurogenic regulation of myosin gene expression in cat jaw‐closing muscles regenerating in fast and slow limb muscle beds. J Muscle Res Cell Motil 9: 59‐72, 1988.
 223.Holloszy J, Coyle E. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56: 831‐838, 1984.
 224.Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 242: 2278‐2282, 1967.
 225.Holm L, Haslund ML, Robach P, van Hall G, Calbet JA, Saltin B, Lundby C. Skeletal muscle myofibrillar and sarcoplasmic protein synthesis rates are affected differently by altitude‐induced hypoxia in native lowlanders. PLoS One 5: e15606, 2010.
 226.Hoppeler H, Flück M. Normal mammalian skeletal muscle and its phenotypic plasticity. J Exp Biol 205: 2143‐2152, 2002.
 227.Hoppeler H, Howald H, Conley K, Lindstedt SL, Claassen H, Vock P, Weibel ER. Endurance training in humans: Aerobic capacity and structure of skeletal muscle. J Appl Physiol 59: 320‐327, 1985.
 228.Hoppeler H, Kleinert E, Schlegel C, Claassen H, Howald H, Kayar SR, Cerretelli P. Morphological adaptations of human skeletal muscle to chronic hypoxia. Int J Sports Med 11(Suppl 1): S3‐S9, 1990.
 229.Hoppeler H, Luthi P, Claassen H, Weibel ER, Howald H. The ultrastructure of the normal human skeletal muscle. A morphometric analysis on untrained men, women and well‐trained orienteers. Pflugers Arch 344: 217‐232, 1973.
 230.Hoppeler H, Vogt M, Weibel ER, Fluck M. Response of skeletal muscle mitochondria to hypoxia. Exp Physiol 88: 109‐119, 2003.
 231.Horman S, Browne G, Krause U, Patel J, Vertommen D, Bertrand L, Lavoinne A, Hue L, Proud C, Rider M. Activation of AMP‐activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12: 1419‐1423, 2002.
 232.Hornberger TA. Mechanotransduction and the regulation of mTORC1 signaling in skeletal muscle. Internat J Biochem Cell Biol 43: 1267‐1276, 2011.
 233.Hornberger TA, Chu WK, Mak YW, Hsiung JW, Huang SA, Chien S. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. Proc Natl Acad Sci U S A 103: 4741‐4746, 2006.
 234.Horstman AM, de Ruiter CJ, van Duijnhoven NT, Hopman MT, de Haan A. Changes in muscle contractile characteristics and jump height following 24 days of unilateral lower limb suspension. Eur J Appl Physiol 112: 135‐144, 2012.
 235.Howald H. Malleability of the motor system: Training for maximizing power output. J Exp Biol 115: 365‐373, 1985.
 236.Howald H, Hoppeler H, Claassen H, Mathieu O, Straub R. Influences of endurance training on the ultrastructural composition of the different muscle fiber types in humans. Pflugers Arch 403: 369‐376, 1985.
 237.Hudson B, Hidalgo C, Saripalli C, Granzier H. Hyperphosphorylation of mouse cardiac titin contributes to transverse aortic constriction‐induced diastolic dysfunction. Circ Res 109: 858‐866, 2011.
 238.Hudson NJ, Franklin CE. Effect of aestivation on muscle characteristics and locomotor performance in the green‐striped burrowing frog, Cyclorana alboguttata. J Comp Physiol [B] 172: 177‐182, 2002.
 239.Hudson NJ, Lehnert SA, Ingham AB, Symonds B, Franklin CE, Harper GS. Lessons from an estivating frog: Sparing muscle protein despite starvation and disuse. Am J Physiol Regul Integr Comp Physiol 290: R836‐R843, 2006.
 240.Huey KA, Roy RR, Baldwin KM, Edgerton VR. Temporal effects of inactivty on myosin heavy chain gene expression in rat slow muscle. Muscle & nerve 24: 517‐526, 2001.
 241.Hughes S, Taylor J, Tapscott S, Gurley C, Carter W, Peterson C. Selective accumulation of MyoD and Myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervations and hormones. Development 118: 1137‐1147, 1993.
 242.Hughes VA, Fiatarone MA, Fielding RA, Kahn BB, Ferrara CM, Shepherd P, Fisher EC, Wolfe RR, Elahi D, Evans WJ. Exercise increases muscle GLUT‐4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264: E855‐E862, 1993.
 243.Hurst JE, Fitts RH. Hindlimb unloading‐induced muscle atrophy and loss of function: Protective effect of isometric exercise. J Appl Physiol 95: 1405‐1417, 2003.
 244.Hyldahl RD, Xin L, Hubal MJ, Moeckel‐Cole S, Chipkin S, Clarkson PM. Activation of nuclear factor‐kappaB following muscle eccentric contractions in humans is localized primarily to skeletal muscle‐residing pericytes. FASEB J 25: 2956‐2966, 2011.
 245.Hynes RO. Integrins: Versatility, modulation, and signaling in cell adhesion. Cell 69: 11‐25, 1992.
 246.Ianuzzo CD, Chen V. Metabolic character of hypertrophied rat muscle. J Appl Physiol 46: 738‐742, 1979.
 247.Ikemoto M, Nikawa T, Takeda S, Watanabe C, Kitano T, Baldwin KM, Izumi R, Nonaka I, Towatari T, Teshima S, Rokutan K, Kishi K. Space shuttle flight (STS‐90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin‐proteasome pathway. FASEB J 15: 1279‐1281, 2001.
 248.Inoue K, Yamasaki S, Fushiki T, Okada Y, Sugimoto E. Androgen receptor antagonist suppresses exercise‐induced hypertrophy of skeletal muscle. Eur J Appl Physiol Occup Physiol 69: 88‐91, 1994.
 249.Irrcher I, Ljubicic V, Hood D. Interactions between ROS and AMP kinase activity in the regulation of PGC‐1α transcription in skeletal muscle cells. Am J Physiol Cell Physiol 296: C116‐C123, 2009.
 250.Ito N, Ruegg UT, Kudo A, Miyagoe‐Suzuki Y, Takeda S. Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy. Nat Med 19: 101‐106, 2013.
 251.Ivy J. Muscle insulin resistance amended with exercise training: Role of GLUT4 expression. Med Sci Sports Exerc 36: 1207‐1211, 2004.
 252.Ivy JL, Brozinick JT, Jr., Torgan CE, Kastello GM. Skeletal muscle glucose transport in obese Zucker rats after exercise training. J Appl Physiol 66: 2635‐2641, 1989.
 253.Izumo S, Nadal‐Ginard B, Mahadavi V. All members of the MHC multigenic family respond to thyroid hormones in a highly tissue‐specific manner. Science 23: 597‐600, 1986.
 254.Jager S, Handschin C, St‐Pierre J, Spiegelman BM. AMP‐activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC‐1alpha. Proc Natl Acad Sci U S A 104: 12017‐12022, 2007.
 255.Jakubiec‐Puka A, Catani C, Carraro U. Myosin heavy‐chain composition in striated muscle after tenotomy. Biochem J 282: 237‐242, 1992.
 256.Jakubiec‐Puka A, Kordowska J, Catani C, Carraro U. Myosin heavy chain isoform composition in striated muscle after denervation and self‐reinnervation. Eur J Biochem 193: 623‐628, 1990.
 257.Jamali AA, Afshar P, Abrams RA, Lieber RL. Skeletal muscle response to tenotomy. Muscle Nerve 23: 851‐862, 2000.
 258.Jansen JK, Lomo T, Nicolaysen K, Westgaard RH. Hyperinnervation of skeletal muscle fibers: Dependence on muscle activity. Science 181: 559‐561, 1973.
 259.Jewell JL, Russell RC, Guan KL. Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 14: 133‐139, 2013.
 260.Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF‐κB activation: Distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 7: 395‐403, 2005.
 261.Kadi F. Adaptation of human skeletal muscle to training and anabolic steroids. Acta Physiol Scand 646: 1‐52, 2000.
 262.Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol 154: 522‐528, 2008.
 263.Kadi F, Eriksson A, Holmner S, Thornell L‐E. Effects of anabolic steroids on the muscle cells of strength‐trained athletes. Med Sci Sports Exerc 31: 1528‐1534, 1999.
 264.Kalista S, Schakman O, Gilson H, Lause P, Demeulder B, Bertrand L, Pende M, Thissen JP. The type 1 insulin‐like growth factor receptor (IGF‐IR) pathway is mandatory for the follistatin‐induced skeletal muscle hypertrophy. Endocrinology 153: 241‐253, 2012.
 265.Kallen R, Sheng Z, Yang J, Chen L, Rogart R, Barchi R. Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle. Neuron 4 233‐242, 1990.
 266.Kang L, Hoh J. Regulation of jaw‐specific isoforms of myosin binding protein‐C and tropomyosin in regenerating cat temporalis muscle innervated by limb fast and slow motor nerves. J Histochem Cytochem 58: 989‐1004, 2010.
 267.Kanter M. Free radicals and exercise: Effects of nutritional antioxidant supplementation. Exerc Sport Sci Rev 23: 375‐397, 1995.
 268.Kavazis A, Talbert E, Smuder A, Hudson M, Nelson, WB, Powers S. Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production. Free Radic Biol Med 46: 842‐850, 2009.
 269.Kemp JG, Blazev R, Stephenson DG, Stephenson GM. Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse. Int J Obes (Lond) 33: 831‐841, 2009.
 270.Kemp TJ, Sadusky TJ, Saltisi F, Carey N, Moss J, Yang SY, Sassoon DA, Goldspink G, Coulton GR. Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch‐responsive ankyrin‐repeat protein. Genomics 66: 229‐241, 2000.
 271.Kim Y, Sainz R, Molenaar P, Summers R. Characterization of β1‐ and β2‐adrenoceptors in rat skeletal muscles. Biochem Pharmacol 429: 1783‐1789, 1991.
 272.Kim YS, Sainz RD. Beta‐adrenergic agonists and hypertrophy of skeletal muscles. Life Sci 50: 397‐407, 1992.
 273.Kirschbaum BJ, Kucher HB, Termin A, Kelly AM, Pette D. Antagonistic effects of chronic low frequency stimulation and thyroid hormone on myosin expression in rat fast‐twitch muscle. J Biol Chem 265: 13974‐13980, 1990.
 274.Kline W, Panaro F, Yang H, Bodine S. Rapamycin inhibits the growth and muscle‐sparing effects of clenbuterol. J Appl Physiol 102: 740‐747, 2007.
 275.Klitgaard H, Bergman O, Betto R, Salviati G, Schiaffino S, Clausen T, Saltin B. Co‐existence of myosin heavy chain I and IIa isoforms in human skeletal muscle fibres with endurance training. Pflugers Arch 416: 470‐472, 1990.
 276.Klitgaard H, Zhou M, Richter E. Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders. Acta Physiol Scand 140: 175‐180, 1990.
 277.Klug G, Reichmann H, Pette D. Rapid reduction in parvalbumin concentration during chronic stimulation of rabbit fast twitch muscle. FEBS Lett 152: 180‐182, 1983.
 278.Kong Y, Flick MJ, Kudla AJ, Konieczny SF. Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD. Mol Cell Biol 17: 4750‐4760, 1997.
 279.Kriketos AD, Pan DA, Lillioja S, Cooney GJ, Baur LA, Milner MR, Sutton JR, Jenkins AB, Bogardus C, Storlien LH. Interrelationships between muscle morphology, insulin action, and adiposity. Am J Physiol 270: R1332‐R1339, 1996.
 280.Krogh A, Lindhard J. The relative value of fat and carbohydrate as sources of muscular energy: With appendices on the correlation between standard metabolism and the respiratory quotient during rest and work. Biochem J 14: 290‐363, 1920.
 281.Kugelberg E, Edstrom L. Differential histochemical effects of muscle contractions on phosphorylase and glycogen in various types of fibres: Relation to fatigue. J Neurol Neurosurg Psychiat 31: 415‐423, 1968.
 282.Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie MJ. Age‐related differences in the dose‐response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 587: 211‐217, 2009.
 283.Kyparos A, Feeback DL, Layne CS, Martinez DA, Clarke MS. Mechanical stimulation of the plantar foot surface attenuates soleus muscle atrophy induced by hindlimb unloading in rats. J Appl Physiol 99: 739‐746, 2005.
 284.Labeit S, Gautel M, Lakey A, Trinick J. Towards a molecular understanding of titin. EMBO J 11: 1711‐1716, 1992.
 285.Lai KM, Gonzalez M, Poueymirou WT, Kline WO, Na E, Zlotchenko E, Stitt TN, Economides AN, Yancopoulos GD, Glass DJ. Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol 24: 9295‐9304, 2004.
 286.Lambert D, Thomas G. Alpha‐adrenoceptor constrictor responses and their modulation in slow‐twitch and fast‐twitch mouse skeletal muscle. J Physiol 563: 821‐829, 2005.
 287.Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. Rapamycin‐induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638‐1643, 2012.
 288.Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, Kristensen J, Brandmeier B, Franzen G, Hedberg B, Gunnarsson LG, Hughes SM, Marchand S, Sejersen T, Richard I, Edstrom L, Ehler E, Udd B, Gautel M. The kinase domain of titin controls muscle gene expression and protein turnover. Science 308: 1599‐1603, 2005.
 289.Langen RC, Haegens A, Vernooy JH, Wouters EF, de Winther MP, Carlsen H, Steele C, Shoelson SE, Schols AM. NF‐kappaB activation is required for the transition of pulmonary inflammation to muscle atrophy. Am J Resp Cell and Mol Biol 47: 288‐297, 2012.
 290.Lantier L, Mounier R, Leclerc J, Pende M, Foretz M, Viollet B. Coordinated maintenance of muscle cell size control by AMP‐activated protein kinase. FASEB J 24: 3555‐3561, 2010.
 291.Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 149: 274‐293, 2012.
 292.Larsson L, Li X, Berg HE, Frontera WR. Effects of removal of weight‐bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflugers Arch 432: 320‐328, 1996.
 293.Laughlin M, Roseguini B. Mechanisms for exercise training‐induced increases in skeletal muscle blood flow capacity: Sprint training versus aerobic endurance training. J Physiol Pharmacol 59(Suppl 7): 71‐88, 2008.
 294.Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, Cianflone K, Sonenberg N. Elevated sensitivity to diet‐induced obesity and insulin resistance in mice lacking 4E‐BP1 and 4E‐BP2. J Clin Invest 117: 387‐396, 2007.
 295.Leberer E, Härtner K, Brandl C, Fujii J, Tada M, MacLennan D, Pette D. Slow/cardiac sarcoplasmic reticulum Ca2+‐ATPase and phospholamban mRNAs are expressed in chronically stimulated rabbit fast‐twitch muscle. Eur J Biochem 185: 51‐54, 1989.
 296.Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, Price SR, Mitch WE, Goldberg AL. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 18: 39‐51, 2004.
 297.Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Ellisman MH, Bodmer R, Bier E, Karin M. Sestrin as a feedback inhibitor of TOR that prevents age‐related pathologies. Science 327: 1223‐1228, 2010.
 298.Lee SJ. Quadrupling muscle mass in mice by targeting TGF‐beta signaling pathways. PLoS ONE 2: e789, 2007.
 299.Lee SJ, Huynh TV, Lee YS, Sebald SM, Wilcox‐Adelman SA, Iwamori N, Lepper C, Matzuk MM, Fan CM. Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci U S A 109: E2353‐E2360, 2012.
 300.Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U S A 98: 9306‐9311, 2001.
 301.Lee‐Young RS, Ayala JE, Hunley CF, James FD, Bracy DP, Kang L, Wasserman DH. Endothelial nitric oxide synthase is central to skeletal muscle metabolic regulation and enzymatic signaling during exercise in vivo. Am J Physiol Regul Integr Comp Physiol 298: R1399‐R1408, 2010.
 302.Leick L, Wojtaszewski JF, Johansen ST, Kiilerich K, Comes G, Hellsten Y, Hidalgo J, Pilegaard H. PGC‐1alpha is not mandatory for exercise‐ and training‐induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab 294: E463‐E474, 2008.
 303.Lepper C, Conway SJ, Fan CM. Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements. Nature 460: 627‐631, 2009.
 304.Leterme D, Cordonnier C, Mounier Y, Falempin M. Influence of chronic stretching upon rat soleus muscle during non‐weight‐bearing conditions. Pflugers Arch 429: 274‐279, 1994.
 305.Levett DZ, Radford EJ, Menassa DA, Graber EF, Morash AJ, Hoppeler H, Clarke K, Martin DS, Ferguson‐Smith AC, Montgomery HE, Grocott MP, Murray AJ. Acclimatization of skeletal muscle mitochondria to high‐altitude hypoxia during an ascent of Everest. FASEB J 26: 1431‐1441, 2012.
 306.Levine S, Kaiser L, Leferovich J, Tikunov B. Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. N Engl J Med 337: 1799‐1806, 1997.
 307.Lexell J, Jarvis J, Downham D, Salmons S. Quantitative morphology of stimulation‐induced damage in rabbit fast‐twitch skeletal muscles. Cell Tissue Res 269: 195‐204, 1992.
 308.Li T, Finch EA, Graham V, Zhang ZS, Ding JD, Burch J, Oh‐hora M, Rosenberg P. STIM1‐Ca(2+) signaling is required for the hypertrophic growth of skeletal muscle in mice. Mol Cell Biol 32: 3009‐3017, 2012.
 309.Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC‐1 family of transcription coactivators. Cell Metab 1: 361‐370, 2005.
 310.Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel‐Duby R, Spiegelman BM. Transcriptional co‐activator PGC‐1 alpha drives the formation of slow‐twitch muscle fibres. Nature 418: 797‐801, 2002.
 311.Lippi G, Franchini M, Banfi G. Biochemistry and physiology of anabolic androgenic steroids doping. Mini Rev Med Chem 11: 362‐373, 2011.
 312.Lira V, Brown D, Lira A, Kavazis A, Soltow Q, Zeanah E, and Criswell D. Nitric oxide and AMPK cooperatively regulate PGC‐1 in skeletal muscle cells. J Physiol 588: 3551‐3566, 2010.
 313.Liu JX, Hoglund AS, Karlsson P, Lindblad J, Qaisar R, Aare S, Bengtsson E, Larsson L. Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100,000‐fold difference in body size. Exp Physiol 94: 117‐129, 2009.
 314.Liu Z, Li G, Kimball SR, Jahn LA, Barrett EJ. Glucocorticoids modulate amino acid‐induced translation initiation in human skeletal muscle. Am J Physiol Endocrinol Metab 287: E275‐E281, 2004.
 315.Liu ZQ, Jahn LA, Long W, Fryburg DA, Wei LP, Barrett EJ. Branched chain amino acids activate messenger ribonucleic acid translation regulatory proteins in human skeletal muscle, and glucocorticoids blunt this action. J Clin Endocrinol and Metabolism 86: 2136‐2143, 2001.
 316.Lo MS, Lin LL, Yao WJ, Ma MC. Training and detraining effects of the resistance vs. endurance program on body composition, body size, and physical performance in young men. J Strength Cond Res 25: 2246‐2254, 2011.
 317.Lofberg E, Gutierrez A, Wernerman J, Anderstam B, Mitch W, Price S, Bergstrom J, Alvestrand A. Effects of high doses of glucocorticoids on free amino acids, ribosomes and protein turnover in human muscle. Eur J Clin Invest 32: 345‐353, 2002.
 318.Lokireddy S, McFarlane C, Ge X, Zhang H, Sze SK, Sharma M, Kambadur R. Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling mechanism during skeletal muscle wasting. Mol Endocrinol 25: 1936‐1949, 2011.
 319.Loschen G, Azzi A, Richter C, Flohe L. Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett 42: 68‐72, 1974.
 320.Loughna PT, Izumo S, Goldspink G, Nadal‐Ginard B. Disuse and passive stretch cause rapid alterations in expression of developmental and adult contractile protein genes in skeletal muscle. Development 109: 217‐223, 1990.
 321.Lu L, Zhou L, Chen EZ, Sun K, Jiang P, Wang L, Su X, Sun H, Wang H. A Novel YY1‐miR‐1 regulatory circuit in skeletal myogenesis revealed by genome‐wide prediction of YY1‐miRNA network. PLoS One 7: e27596, 2012.
 322.Luff AR. Dynamic properties of fast and slow skeletal muscles in the cat and rat following cross‐reinnervation. J Physiol 248: 83‐96, 1975.
 323.Lunde IG, Anton SL, Bruusgaard JC, Rana ZA, Ellefsen S, Gundersen K. Hypoxia inducible factor 1 links fast‐patterned muscle activity and fast muscle phenotype in rats. J Physiol 589: 1443‐1454, 2011.
 324.Luther P. The vertebrate muscle Z‐disc: Sarcomere anchor for structure and signalling. J Muscle Res Cell Motil 30: 171‐185, 2009.
 325.Luthi JM, Howald H, Claassen H, Rosler K, Vock P, Hoppeler H. Structural changes in skeletal muscle tissue with heavy‐resistance exercise. Int J Sports Med 7: 123‐127, 1986.
 326.Lynch GS, Hayes A, Campbell SP, Williams DA. Effects of beta2‐agonist administration and exercise on contractile activation of skeletal muscle fibers. J Appl Physiol 81: 1610‐1618, 1996.
 327.Lynch GS, Ryall JG. Role of beta‐adrenoceptor signaling in skeletal muscle: Implications for muscle wasting and disease. Physiol Rev 88: 729‐767, 2008.
 328.Lyons GE, Kelly AM, Rubinstein NA. Testosterone‐induced changes in contractile protein isoforms in the sexually dimorphic temporalis muscle of the guinea pig. J Biol Chem 261: 13278‐13284, 1986.
 329.Ma XM, Blenis J. Molecular mechanisms of mTOR‐mediated translational control. Nat Rev Mol Cell Biol 10: 307‐318, 2009.
 330.Mackey A, Kjaer M, Dandanell S, Mikkelsen K, Holm L, Dossing S, Kadi F, Koskinen S, Jensen C, Schroder H, Langberg H. The influence of antiinflammatory medication on exercise‐induced myogenic precursor cell responses in humans. J Appl Physiol 103: 425‐431, 2007.
 331.Mackova E, Hnik P. Compensatory muscle hypertrophy induced by tenotomy of synergists is not true working hypertrophy. Physiol Bohemoslov 22: 43‐49, 1973.
 332.Mahdavi V, Izumo S, Nadal‐Ginard B. Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family. Circ Res 60: 804‐814, 1987.
 333.Maier A, Gambke B, Pette D. Degeneration‐regeneration as a mechanism contributing to the fast to slow conversion of chronically stimulated fast‐twitch rabbit muscle. Cell Tissue Res 244: 635‐643, 1986.
 334.Maltais F, Sullivan MJ, LeBlanc P, Duscha BD, Schachat FH, Simard C, Blank JM, Jobin J. Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD. Eur Respir J 13: 850‐854, 1999.
 335.Maltin CA, Hay SM, Delday MI, Lobley GE, Reeds PJ. Theaction of the beta‐agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles. Biochem J 261: 965‐971, 1989.
 336.Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6: 458‐471, 2007.
 337.Marino JS, Tausch BJ, Dearth CL, Manacci MV, McLoughlin TJ, Rakyta SJ, Linsenmayer MP, Pizza FX. Beta2‐integrins contribute to skeletal muscle hypertrophy in mice. Am J Physiol Cell Physiol 295: C1026‐C1036, 2008.
 338.Martin T, Stein R, Hoeppner P, Reid D. Influence of electrical stimulation on the morphological and metabolic properties of paralyzed muscle. J Appl Physiol 72: 1401‐1406, 1992.
 339.Martinelli M, Winterhalder R, Cerretelli P, Howald H, Hoppeler H. Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans. Experientia 46: 672‐676, 1990.
 340.Martins KJ, St‐Louis M, Murdoch GK, MacLean IM, McDonald P, Dixon WT, Putman CT, Michel RN. Nitric oxide synthase inhibition prevents activity‐induced calcineurin‐NFATc1 signalling and fast‐to‐slow skeletal muscle fibre type conversions. J Physiol 590: 1427‐1442, 2012.
 341.Mascher H, Tannerstedt J, Brink‐Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E. Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF‐1 in human skeletal muscle. Am J Physiol Endocrinol Metab 294: E43‐E51, 2008.
 342.Mason SD, Howlett RA, Kim MJ, Olfert IM, Hogan MC, McNulty W, Hickey RP, Wagner PD, Kahn CR, Giordano FJ, Johnson RS. Loss of skeletal muscle HIF‐1alpha results in altered exercise endurance. PLoS Biol 2: e288, 2004.
 343.Mason SD, Rundqvist H, Papandreou I, Duh R, McNulty WJ, Howlett RA, Olfert IM, Sundberg CJ, Denko NC, Poellinger L, Johnson RS. HIF‐1alpha in endurance training: Suppression of oxidative metabolism. Am J Physiol Regul Integr Comp Physiol 293: R2059‐R2069, 2007.
 344.McBride A, Ghilagaber S, Nikolaev A, Hardie DG. The glycogen‐binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor. Cell Metab 9: 23‐34, 2009.
 345.McCall GE, Byrnes WC, Dickinson A, Pattany PM, Fleck SJ. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. J Appl Physiol 81: 2004‐2012, 1996.
 346.McCarthy JJ, Esser KA, Peterson CA, Dupont‐Versteegden EE. Evidence of MyomiR network regulation of beta‐myosin heavy chain gene expression during skeletal muscle atrophy. Physiol Genomics 39: 219‐226, 2009.
 347.McCarthy JJ, Mula J, Miyazaki M, Erfani R, Garrison K, Farooqui AB, Srikuea R, Lawson BA, Grimes B, Keller C, Van Zant G, Campbell KS, Esser KA, Dupont‐Versteegden EE, Peterson CA. Effective fiber hypertrophy in satellite cell‐depleted skeletal muscle. Development 138: 3657‐3666, 2011.
 348.McDonald KS, Fitts RH. Effect of hindlimb unweighting on single soleus fiber maximal shortening velocity and ATPase activity. J Appl Physiol 74: 2949‐2957, 1993.
 349.McKoy G, Ashley W, Mander J, Yang SY, Williams N, Russell B, Goldspink G. Expression of insulin growth factor‐1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. J Physiol 516: 583‐592, 1999.
 350.McKoy G, Hou Y, Yang SY, Vega Avelaira D, Degens H, Goldspink G, Coulton GR. Expression of Ankrd2 in fast and slow muscles and its response to stretch are consistent with a role in slow muscle function. J Appl Physiol 98: 2337‐2343; discussion 2320, 2005.
 351.McLoon LK, Park HN, Kim JH, Pedrosa‐Domellof F, Thompson LV. A continuum of myofibers in adult rabbit extraocular muscle: Force, shortening velocity, and patterns of myosin heavy chain colocalization. J Appl Physiol 111: 1178‐1189, 2011.
 352.McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF‐beta superfamily member. Nature 387: 83‐90, 1997.
 353.Meissner JD, Freund R, Krone D, Umeda PK, Chang KC, Gros G, Scheibe RJ. Extracellular signal‐regulated kinase 1/2‐mediated phosphorylation of p300 enhances myosin heavy chain I/beta gene expression via acetylation of nuclear factor of activated T cells c1. Nucleic Acids Res 39: 5907‐5925, 2011.
 354.Mendell LM, Collins WF III, Munson JB. Retrograde determination of motoneuron properties and their synaptic input. J Neurobiol 25: 707‐721, 1994.
 355.Meyer H. p97 complexes as signal integration hubs. BMC biology 10: 48, 2012.
 356.Mian I, Pierre‐Louis WS, Dole N, Gilberti RM, Dodge‐Kafka K, Tirnauer JS. LKB1 destabilizes microtubules in myoblasts and contributes to myoblast differentiation. PLoS One 7: e31583, 2012.
 357.Midrio M. The denervated muscle: Facts and hypotheses. A historical review. Eur J Appl Physiol 98: 1‐21, 2006.
 358.Midrio M, Danieli Betto D, Betto R, Noventa D, Antico F. Cordotomy‐denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat. Exp Neurol 100: 216‐236, 1988.
 359.Midrio M, Danieli‐Betto D, Megighian A, Betto R. Early effects of denervation on sarcoplasmic reticulum properties of slow‐twitch rat muscle fibres. Pflugers Arch 434: 398‐405, 1997.
 360.Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of training on the dose‐response relationship for insulin action in men. J Appl Physiol 66: 695‐703, 1989.
 361.Mikkelsen U, Langberg H, Helmark I, Skovgaard D, Andersen L, Kjaer M, Mackey A. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise. J Appl Physiol 107: 1600‐1611, 2009.
 362.Millay DP, Goonasekera SA, Sargent MA, Maillet M, Aronow BJ, Molkentin JD. Calcium influx is sufficient to induce muscular dystrophy through a TRPC‐dependent mechanism. Proc Natl Acad Sci U S A 106: 19023‐19028, 2009.
 363.Minamisawa S, Hoshijima M, Chu G, Ward CA, Frank K, Gu Y, Martone ME, Wang Y, Ross J, Jr., Kranias EG, Giles WR, Chien KR. Chronic phospholamban‐sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99: 313‐322, 1999.
 364.Miura S, Kai Y, Ono M, Ezaki O. Overexpression of peroxisome proliferator‐activated receptor gamma coactivator‐1alpha down‐regulates GLUT4 mRNA in skeletal muscles. J Biol Chem 278: 31385‐31390, 2003.
 365.Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15: 1101‐1111, 2004.
 366.Mofarrahi M, Sigala I, Guo Y, Godin R, Davis EC, Petrof B, Sandri M, Burelle Y, Hussain SN. Autophagy and skeletal muscles in sepsis. PLoS One 7: e47265, 2012.
 367.Morey‐Holton ER, Globus RK. Hindlimb unloading rodent model: Technical aspects. J Appl Physiol 92: 1367‐1377, 2002.
 368.Mounier R, Lantier L, Leclerc J, Sotiropoulos A, Pende M, Daegelen D, Sakamoto K, Foretz M, Viollet B. Important role for AMPKalpha1 in limiting skeletal muscle cell hypertrophy. FASEB J 23: 2264‐2273, 2009.
 369.Moylan J, Reid M. Oxidative stress, chronic disease, and muscle wasting. Muscle Nerve 35: 411‐429, 2007.
 370.Mujika I, Padilla S. Detraining: Loss of training‐induced physiological and performance adaptations. Part I: Short term insufficient training stimulus. Sports Med 30: 79‐87, 2000.
 371.Mujika I, Padilla S. Detraining: Loss of training‐induced physiological and performance adaptations. Part II: Long term insufficient training stimulus. Sports Med 30: 145‐154, 2000.
 372.Mujika I, Padilla S. Cardiorespiratory and metabolic characteristics of detraining in humans. Med Sci Sports Exerc 33: 413‐421, 2001.
 373.Munson JB, Foehring RC, Mendell LM, Gordon T. Fast‐to‐slow conversion following chronic low‐frequency activation of medial gastrocnemius muscle in cats. II. Motoneuron properties. J Neurophysiol 77: 2605‐2615, 1997.
 374.Musacchia XJ, Fagette S. Weightlessness simulations for cardiovascular and muscle systems: Validity of rat models. J Gravit Physiol 4: 49‐59, 1997.
 375.Musacchia XJ, Steffen JM, Deavers DR. Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia. Aviat Space Environ Med 54: 1015‐1020, 1983.
 376.Muscatello U, Margreth A, Aloisi M. On the differential response of sarcoplasm and myoplasm to denervation in frog muscle. J Cell Biol 27: 1‐24, 1965.
 377.Narici M, de Boer M. Disuse of the musculo‐skeletal system in space and on earth. Eur J Appl Physiol 111: 403‐420 2011.
 378.Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARdelta agonists are exercise mimetics. Cell 134: 405‐415, 2008.
 379.Narkar VA, Fan W, Downes M, Yu RT, Jonker JW, Alaynick WA, Banayo E, Karunasiri MS, Lorca S, Evans RM. Exercise and PGC‐1alpha‐independent synchronization of type I muscle metabolism and vasculature by ERRgamma. Cell Metabolism 13: 283‐293, 2011.
 380.Navegantes LC, Resano NM, Baviera AM, Migliorini RH, Kettelhut IC. CL 316,243, a selective beta3‐adrenergic agonist, inhibits protein breakdown in rat skeletal muscle. Pflugers Arch 45: 617‐624, 2006.
 381.Nelson OL, Robbins CT, Wu Y, Granzier H. Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears. Am J Physiol Heart Circ Physiol 295: H366‐H371, 2008.
 382.Neufer PD. The effect of detraining and reduced training on the physiological adaptations to aerobic exercise training. Sports Med 8: 302‐320, 1989.
 383.Nicastro H, Zanchi NE, da Luz CR, Chaves DF, and Lancha AH, Jr. An experimental model for resistance exercise in rodents. J Biomed Biotechnol 2012: 457065, 2012.
 384.Nishijo K, Hosoyama T, Bjornson CR, Schaffer BS, Prajapati SI, Bahadur AN, Hansen MS, Blandford MC, McCleish AT, Rubin BP, Epstein JA, Rando TA, Capecchi MR, Keller C. Biomarker system for studying muscle, stem cells, and cancer in vivo. FASEB J 23: 2681‐2690, 2009.
 385.Norman B, Esbjornsson M, Rundqvist H, Osterlund T, von Walden F, Tesch PA. Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol 106: 959‐965, 2009.
 386.Nozais M, Lompre AM, Janmot C, D'Albis A. Sarco(endo)plasmic reticulum Ca2+ pump and metabolic enzyme expression in rabbit fast‐type and slow‐type denervated skeletal muscles. A time course study. Eur J Biochem 238: 807‐812, 1996.
 387.Nuhr M, Crevenna R, Gohlsch B, Bittner C, Pleiner J, Wiesinger G, Fialka‐Moser V, Quittan M, Pette D. Functional and biochemical properties of chronically stimulated human skeletal muscle. Eur J Appl Physiol 89: 202‐208, 2003.
 388.O'Connor RS, Pavlath GK. Point:Counterpoint: Satellite cell addition is/is not obligatory for skeletal muscle hypertrophy. J Appl Physiol 103: 1099‐1100, 2007.
 389.Ohanna M, Sobering AK, Lapointe T, Lorenzo L, Praud C, Petroulakis E, Sonenberg N, Kelly PA, Sotiropoulos A, Pende M. Atrophy of S6K1(‐/‐) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 7: 286‐294, 2005.
 390.Ohlendieck K, Briggs F, Lee K, Wechsler A, Campbell K. Analysis of excitation‐contraction‐coupling components in chronically stimulated canine skeletal muscle. Eur J Biochem 202: 739‐747, 1991.
 391.Olesen J, Kiilerich K, Pilegaard H. PGC‐1alpha‐mediated adaptations in skeletal muscle. Pflugers Archiv 460: 153‐162, 2010.
 392.Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H. Skeletal muscle PGC‐1alpha is required for maintaining an acute LPS‐induced TNFalpha response. PLoS One 7: e32222, 2012.
 393.Olfert I, Howlett R, Wagner P, Breen E. Myocyte vascular endothelial growth factor is required for exercise‐induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 299: R1059‐R1067, 2010.
 394.Osler ME, Zierath JR. Adenosine 5'‐monophosphate‐activated protein kinase regulation of fatty acid oxidation in skeletal muscle. Endocrinology 149: 935‐941, 2008.
 395.Pallafacchina G, Blaauw B, Schiaffino S. Role of satellite cells in muscle growth and maintenance of muscle mass. Nutr Metab Cardiovasc Dis 2012.
 396.Pallafacchina G, Calabria E, Serrano AL, Kalhovde JM, Schiaffino S. A protein kinase B‐dependent and rapamycin‐sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci U S A 99: 9213‐9218, 2002.
 397.Pappone P. Voltage‐clamp experiments in normal and denervated mammalian skeletal muscle fibres. J Physiol 306: 377‐410, 1980.
 398.Parikh H, Nilsson E, Ling C, Poulsen P, Almgren P, Nittby H, Eriksson KF, Vaag A, Groop LC. Molecular correlates for maximal oxygen uptake and type 1 fibers. Am J Physiol Endocrinol Metab 294: E1152‐E1159, 2008.
 399.Parsons SA, Millay DP, Wilkins BJ, Bueno OF, Tsika GL, Neilson JR, Liberatore CM, Yutzey KE, Crabtree GR, Tsika RW, Molkentin JD. Genetic loss of calcineurin blocks mechanical overload‐induced skeletal muscle fiber type switching but not hypertrophy. J Biol Chem 279: 26192‐26200, 2004.
 400.Pattullo MC, Cotter MA, Cameron NE, Barry JA. Effects of lengthened immobilization on functional and histochemical properties of rabbit tibialis anterior muscle. Exp Physiol 77: 433‐442, 1992.
 401.Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, Kumar A. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol 191: 1395‐1411, 2010.
 402.Pavlath GK, Rich K, Webster SG, Blau HM. Localization of muscle gene products in nuclear domains. Nature 337: 570‐573, 1989.
 403.Pavy‐Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J. From space to Earth: Advances in human physiology from 20 years of bed rest studies (1986‐2006). Eur J Appl Physiol 101: 143‐194, 2007.
 404.Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE. The orphan nuclear receptor, NOR‐1, is a target of beta adrenergic signaling in skeletal muscle. Endocrinology 147: 5217‐5227, 2006.
 405.Pellegrino MA, Canepari M, D'Antona G, Reggiani C, Bottinelli R. Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles. J Physiol 546: 677‐689, 2003.
 406.Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand‐Brustel Y, Klumperman J, Thorens B, Thomas G. Hypoinsulinaemia, glucose intolerance and diminished beta‐cell size in S6K1‐deficient mice. Nature 408: 994‐997, 2000.
 407.Peterson JM, Bakkar N, Guttridge DC. NF‐kappaB signaling in skeletal muscle health and disease. Curr Top Dev Biol 96: 85‐119, 2011.
 408.Petrella JK, Kim JS, Mayhew DL, Cross JM, Bamman MM. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell‐mediated myonuclear addition: A cluster analysis. J Appl Physiol 104: 1736‐1742, 2008.
 409.Pette D. Historical Perspectives: Plasticity of mammalian skeletal muscle. J Appl Physiol 90: 1119‐1124, 2001.
 410.Pette D, Smith M, Staudte H, Vrbová G. Effects of long‐term electrical stimulation on some contractile and metabolic characteristics of fast rabbit muscles. Pflugers Arch 338: 257‐272, 1973.
 411.Pette D, Staron RS. Mammalian skeletal muscle fiber type transitions. Int Rev Cytol 170: 143‐223, 1997.
 412.Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech 50: 500‐509, 2000.
 413.Pette D, Vrobva G. Adaptation of mammalian skeletal muscle fibers to chronic electrical stimulation. Rev Physiol Biochem Pharmacol 120: 1992.
 414.Piao YJ, Seo YH, Hong F, Kim JH, Kim YJ, Kang MH, Kim BS, Jo SA, Jo I, Jue DM, Kang I, Ha J, Kim SS. Nox 2 stimulates muscle differentiation via NF‐kappaB/iNOS pathway. Free Radic Biol Med 38: 989‐1001, 2005.
 415.Piccirillo R, Goldberg AL. The p97/VCP ATPase is critical in muscle atrophy and the accelerated degradation of muscle proteins. EMBO J 31: 3334‐3350, 2012.
 416.Pines M, Das R, Ellis SJ, Morin A, Czerniecki S, Yuan L, Klose M, Coombs D, Tanentzapf G. Mechanical force regulates integrin turnover in Drosophila in vivo. Nat Cell Biol 14: 935‐943, 2012.
 417.Polla B, Bottinelli R, Sandoli D, Sardi C, Reggiani C. Cortisone‐induced changes in myosin heavy chain distribution in respiratory and hindlimb muscles. Acta Physiol Scand 151: 353‐361, 1994.
 418.Polla B, Cappelli V, Morello F, Pellegrino M, Boschi F, Pastoris O, Reggiani C. Effects of the beta2‐agonist clenbuterol on respiratory and limb muscles of weaning rats. Am J Physiol Regul Integr Comp Physiol 280 R862‐R869, 2001.
 419.Powers S, Kavazis A, McClung J. Oxidative stress and disuse muscle atrophy. J Appl Physiol 102: 2389‐2397, 2007.
 420.Powers SK, and Jackson MJ. Exercise‐induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol Rev 88: 1243‐1276, 2008.
 421.Powers SK, Talbert EE, Adhihetty PJ. Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle. J Physiol 589: 2129‐2138, 2011.
 422.Powers SK, Wiggs MP, Duarte JA, Zergeroglu AM, Demirel HA. Mitochondrial signaling contributes to disuse muscle atrophy. Am J Physiol Endocrinol Metab 303: E31‐E39, 2012.
 423.Prado LG, Makarenko I, Andresen C, Kruger M, Opitz CA, Linke WA. Isoform diversity of giant proteins in relation to passive and active properties of rabbit skeletal muscles. J Gen Physiol 126: 461‐480, 2005.
 424.Puchner EM, Alexandrovich A, Kho AL, Hensen U, Schafer LV, Brandmeier B, Grater F, Grubmuller H, Gaub HE, Gautel M. Mechanoenzymatics of titin kinase. Proc Natl Acad Sci U S A 105: 13385‐13390, 2008.
 425.Pyle WG, Solaro RJ. At the crossroads of myocardial signaling: The role of Z‐discs in intracellular signaling and cardiac function. Circ Res 94: 296‐305, 2004.
 426.Quiat D, Voelker KA, Pei J, Grishin NV, Grange RW, Bassel‐Duby R, Olson EN. Concerted regulation of myofiber‐specific gene expression and muscle performance by the transcriptional repressor Sox6. Proc Natl Acad Sci U S A 108: 10196‐10201, 2011.
 427.Quy PN, Kuma A, Pierre P, Mizushima N. Proteasome‐dependent activation of mammalian target of rapamycin complex 1 (mTORC1) is essential for autophagy suppression and muscle remodeling following denervation. J Cell Biol 288: 1125‐1134, 2013.
 428.Raffaello A, Milan G, Masiero E, Carnio S, Lee D, Lanfranchi G, Goldberg AL, Sandri M. JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy. J Cell Biol 191: 101‐113, 2010.
 429.Rafuse V, Milner L, Landmesser L. Selective innervation of fast and slow muscle regions during early chick neuromuscular development. J Neurosci 16: 6864‐6877, 1996.
 430.Raney MA, Turcotte LP. Evidence for the involvement of CaMKII and AMPK in Ca2+‐dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle. J Appl Physiol 104: 1366‐1373, 2008.
 431.Rasbach KA, Gupta RK, Ruas JL, Wu J, Naseri E, Estall JL, Spiegelman BM. PGC‐1alpha regulates a HIF2alpha‐dependent switch in skeletal muscle fiber types. Proc Natl Acad Sci U S A 107: 21866‐21871, 2010.
 432.Reed SA, Sandesara PB, Senf SM, Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J 26: 987‐1000, 2012.
 433.Reich KA, Chen YW, Thompson PD, Hoffman EP, Clarkson PM. Forty‐eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans. J Appl Physiol 109: 1404‐1415, 2010.
 434.Reichmann H, Hoppeler H, Mathieu‐Costello O, von Bergen F, Pette D. Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflugers Arch 404: 1‐9, 1985.
 435.Reid B, Slater CR, Bewick GS. Synaptic vesicle dynamics in rat fast and slow motor nerve terminals. J Neuroscience 19: 2511‐2521, 1999.
 436.Reynafarje B. Myoglobin content and enzymatic activity of muscle and altitude adaptation. J Appl Physiol 17: 301‐305, 1962.
 437.Rhee H, Hoh J. Immunohistochemical analysis of the affects of cross‐innervation of murine thyroarytenoid and sternohyoid muscles. J Histochem Cytochem 58: 1057‐1065, 2010.
 438.Rhee H, Lucas C, Hoh J. Fiber types in rat laryngeal muscles and their transformations after denervation and reinnervation. J Histochem Cytochem 52: 581‐590, 2004.
 439.Riso E, Ahtikoski A, Alev K, Kaasik P, Pehme A, Seene T. Relationship between extracellular matrix, contractile apparatus, muscle mass and strength in case of glucocorticoid myopathy. J Steroid Biochem Mol Biol 108: 117‐120, 2008.
 440.Risson V, Mazelin L, Roceri M, Sanchez H, Moncollin V, Corneloup C, Richard‐Bulteau H, Vignaud A, Baas D, Defour A, Freyssenet D, Tanti JF, Le‐Marchand‐Brustel Y, Ferrier B, Conjard‐Duplany A, Romanino K, Bauche S, Hantai D, Mueller M, Kozma SC, Thomas G, Ruegg MA, Ferry A, Pende M, Bigard X, Koulmann N, Schaeffer L, Gangloff YG. Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy. J Cell Biol 187: 859‐874, 2009.
 441.Roatta S, Farina D. Sympathetic activation by the cold pressor test does not increase the muscle force generation capacity. J Appl Physiol 110: 1526‐1533, 2011.
 442.Romanello V, Sandri M. Mitochondrial biogenesis and fragmentation as regulators of muscle protein degradation. Current Hypertens Rep 12: 433‐439, 2010.
 443.Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ. Mediation of IGF‐1‐induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3: 1009‐1013, 2001.
 444.Rosenblatt JD, Yong D, Parry DJ. Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17: 608‐613, 1994.
 445.Rossi AC, Mammucari C, Argentini C, Reggiani C, Schiaffino S. Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles. J Physiol 588: 353‐364, 2010.
 446.Rourke BC, Yokoyama Y, Milsom WK, Caiozzo VJ. Myosin isoform expression and MAFbx mRNA levels in hibernating golden‐mantled ground squirrels (Spermophilus lateralis). Physiol Biochem Zool 77: 582‐593, 2004.
 447.Roussel D, Lhenry F, Ecochard L, Sempore B, Rouanet J, R. F. Differential effects of endurance training and creatine depletion on regional mitochondrial adaptations in rat skeletal muscle. Biochem J 350: 547‐553, 2000.
 448.Roy R, Edgerton V. Neurobiological perspective of spasticity as occurs after a spinal cord injury. Exp Neurol 235: 116‐122, 2012.
 449.Roy RR, Meadows ID, Baldwin KM, Edgerton VR. Functional significance of compensatory overloaded rat fast muscle. J Appl Physiol 52: 473‐478, 1982.
 450.Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, Spiegelman BM. A PGC‐1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151: 1319‐1331, 2012.
 451.Ryall J, Lynch G. The potential and the pitfalls of beta‐adrenoceptor agonists for the management of skeletal muscle wasting. Pharmacol Ther 120: 219‐232, 2008.
 452.Salmons S, Vrbová G. The influence of activity on some contractile characteristics of mammalian fast and slow muscles. J Physiol 201: 535‐549, 1969.
 453.Salvatori S, Damiani E, Zorzato F, Volpe P, Pierobon S, Quaglino D, Jr., Salviati G, Margreth A. Denervation‐induced proliferative changes of triads in rabbit skeletal muscle. Muscle Nerve 11: 1246‐1259, 1988.
 454.Sambasivan R, Gayraud‐Morel B, Dumas G, Cimper C, Paisant S, Kelly R, Tajbakhsh S. Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell 16: 810‐821, 2009.
 455.Sambasivan R, Yao R, Kissenpfennig A, Van Wittenberghe L, Paldi A, Gayraud‐Morel B, Guenou H, Malissen B, Tajbakhsh S, Galy A. Pax7‐expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development 138: 3647‐3656, 2011.
 456.Sandona D, Desaphy JF, Camerino GM, Bianchini E, Ciciliot S, Danieli‐Betto D, Dobrowolny G, Furlan S, Germinario E, Goto K, Gutsmann M, Kawano F, Nakai N, Ohira T, Ohno Y, Picard A, Salanova M, Schiffl G, Blottner D, Musaro A, Ohira Y, Betto R, Conte D, Schiaffino S. Adaptation of mouse skeletal muscle to long‐term microgravity in the MDS mission. PLoS One 7: e33232, 2012.
 457.Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL, Spiegelman BM. PGC‐1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy‐specific gene transcription. Proc Natl Acad Sci U S A 103: 16260‐16265, 2006.
 458.Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL. Foxo transcription factors induce the atrophy‐related ubiquitin ligase atrogin‐1 and cause skeletal muscle atrophy. Cell 117: 399‐412, 2004.
 459.Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, Sandri M. Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol 296: C1248‐C1257, 2009.
 460.Satta A, Migliori GB, Spanevello A, Neri M, Bottinelli R, Canepari M, Pellegrino MA, Reggiani C. Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Eur Respir J 10: 2853‐2860, 1997.
 461.Sayer AA, Dennison EM, Syddall HE, Gilbody HJ, Phillips DI, Cooper C. Type 2 diabetes, muscle strength, and impaired physical function: The tip of the iceberg? Diabetes Care 28: 2541‐2542, 2005.
 462.Schiaffino S. Fibre types in skeletal muscle: A personal account. Acta physiologica 199: 451‐463, 2010.
 463.Schiaffino S, Bormioli SP, Aloisi M. Cell proliferation in rat skeletal muscle during early stages of compensatory hypertrophy. Virchows Arch B Cell Pathol 11: 268‐273, 1972.
 464.Schiaffino S, Bormioli SP, Aloisi M. The fate of newly formed satellite cells during compensatory muscle hypertrophy. Virchows Arch B Cell Pathol 21: 113‐118, 1976.
 465.Schiaffino S, Dyar K, Ciciliot S, Blaauw B, Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J (in press), 2013.
 466.Schiaffino S, Gorza L, Pitton G, Saggin L, Ausoni S, Sartore S, Lomo T. Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle. Dev Biol 127: 1‐11, 1988.
 467.Schiaffino S, Mammucari C. Regulation of skeletal muscle growth by the IGF1‐Akt/PKB pathway: Insights from genetic models. Skeletal muscle 1: 4, 2011.
 468.Schiaffino S, Reggiani C. Myosin isoforms in mammalian skeletal muscle. J Appl Physiol 77: 493‐501, 1994.
 469.Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: Gene regulation and functional significance. Physiol Rev 76: 371‐423, 1996.
 470.Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev 91: 1447‐1531, 2011.
 471.Schiaffino S, Sandri M, Murgia M. Activity‐dependent signaling pathways controlling muscle diversity and plasticity. Physiology (Bethesda) 22: 269‐278, 2007.
 472.Schoenfeld B. Does exercise‐induced muscle damage play a role in skeletal muscle hypertrophy? J Strength Cond Res 26: 1441‐1453, 2012.
 473.Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M. Global quantification of mammalian gene expression control. Nature 473: 337‐342, 2011.
 474.Seene T, Kaasik P, Pehme A, Alev K, Riso EM. The effect of glucocorticoids on the myosin heavy chain isoforms' turnover in skeletal muscle. J Steroid BiochemMol Biol 86: 201‐206, 2003.
 475.Seiden D. Quantitative analysis of muscle cell changes in compensatory hypertrophy and work‐induced hypertrophy. Am J Anat 145: 459‐465, 1976.
 476.Seko Y, Takahashi N, Tobe K, Kadowaki T, Yazaki Y. Pulsatile stretch activates mitogen‐activated protein kinase (MAPK) family members and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes. Biochem Biophys Res Commun 259: 8‐14, 1999.
 477.Selvaraj S, Sun Y, Watt JA, Wang S, Lei S, Birnbaumer L, Singh BB. Neurotoxin‐induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J Clin Invest 122: 1354‐1367, 2012.
 478.Semenza G, Nejfelt M, Chi S, Antonarakis S. Hypoxia‐inducible nuclear factors bind to an enhancer located 3' to the human erythropoietin gene. Proc Natl Acad Sci U S A 88: 5680‐5684, 1991.
 479.Semenza GL. Hydroxylation of HIF‐1: oxygen sensing at the molecular level. Physiology (Bethesda) 19: 176‐182, 2004.
 480.Serrano AL, Murgia M, Pallafacchina G, Calabria E, Coniglio P, Lomo T, Schiaffino S. Calcineurin controls nerve activity‐dependent specification of slow skeletal muscle fibers but not muscle growth. Proc Natl Acad Sci U S A 98: 13108‐13113, 2001.
 481.Shafiq SA, Gorycki MA, Asiedu SA, Milhorat AT. Tenotomy. Effect on the fine structure of the soleus of the rat. Arch Neurol 20: 625‐633, 1969.
 482.Shah O, Kimball S, Jefferson L. Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle. Am J Physiol Endocrinol and Metab 278: E76‐E82, 2000a.
 483.Shah O, Kimball S, Jefferson L. Among translational effectors, p70S6k is uniquely sensitive to inhibition by glucocorticoids. Biochemical J 347: 389‐397, 2000b.
 484.Shavlakadze T, Chai J, Maley K, Cozens G, Grounds G, Winn N, Rosenthal N, Grounds MD. A growth stimulus is needed for IGF‐1 to induce skeletal muscle hypertrophy in vivo. J Cell Science 123: 960‐971, 2010.
 485.Shen T, Liu Y, Contreras M, Hernandez‐Ochoa EO, Randall WR, Schneider MF. DNA binding sites target nuclear NFATc1 to heterochromatin regions in adult skeletal muscle fibers. Histochem Cell Biol 134: 387‐402, 2010.
 486.Shi J, Luo L, Eash J, Ibebunjo C, Glass DJ. The SCF‐Fbxo40 complex induces IRS1 ubiquitination in skeletal muscle, limiting IGF1 signaling. Developmental cell 21: 835‐847, 2011.
 487.Shoepe TC, Stelzer JE, Garner DP, Widrick JJ. Functional adaptability of muscle fibers to long‐term resistance exercise. Med Sci Sports Exerc 35: 944‐951, 2003.
 488.Shortreed KE, Krause MP, Huang JH, Dhanani D, Moradi J, Ceddia RB, Hawke TJ. Muscle‐specific adaptations, impaired oxidative capacity and maintenance of contractile function characterize diet‐induced obese mouse skeletal muscle. PLoS One 4: e7293, 2009.
 489.Sillence MN, Matthews ML, Spiers WG, Pegg GG, and Lindsay DB. Effects of clenbuterol, ICI118551 and sotalol on the growth ofcardiac and skeletal muscle and on beta2‐adrenoceptor density infemale rats. Naunyn‐Schmiedebergs Arch Pharmacol 344: 449‐453, 1991.
 490.Simoneau J, Pette D. Species‐specific effects of chronic nerve stimulation upon tibialis anterior muscle in mouse, rat, guinea pig, and rabbit. Pflugers Arch 412: 86‐92, 1988.
 491.Simonides W, van Hardeveld C. Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle. Thyroid 18: 205‐216, 2008.
 492.Smith L, Lee K, Ward S, Chambers H, Lieber R. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length. J Physiol 589: 2625‐2639, 2011.
 493.Smith M, Reid M. Redox modulation of contractile function in respiratory and limb skeletal muscle. Respir Physiol Neurobiol 151: 229‐241, 2006.
 494.Soltow QA, Betters JL, Sellman JE, Lira VA, Long JH, Criswell DS. Ibuprofen inhibits skeletal muscle hypertrophy in rats. Med Sci Sports Exerc 38: 840‐846, 2006.
 495.Sonnet C, Lafuste P, Arnold L, Brigitte M, Poron F, Authier FJ, Chretien F, Gherardi RK, Chazaud B. Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems. J Cell Sci 119: 2497‐2507, 2006.
 496.Sreter F, Lopez J, Alamo L, Mabuchi K, Gergely J. Changes in intracellular ionized Ca concentration associated with muscle fiber type transformation. Am J Physiol Cell Physiol 253: C296‐C300, 1987.
 497.Sreter FA, Luff AR, Gergely J. Effect of cross‐reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit. J Gen Physiol 66: 811‐821, 1975.
 498.St‐Amand J, Yoshioka M, Nishida Y, Tobina T, Shono N, Tanaka H. Effects of mild‐exercise training cessation in human skeletal muscle. Eur J Appl Physiol 112: 853‐869, 2012.
 499.St‐Pierre J, Buckingham J, Roebuck S, and Brand M. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277: 44784‐44790, 2002.
 500.Steffen JM, Koebel DA, Musacchia XJ, Milsom WK. Morphometric and metabolic indices of disuse in muscles of hibernating ground squirrels. Comp Biochem Physiol B 99: 815‐819, 1991.
 501.Stein T, Leskiw K, Schulter M, Donaldson M, Larina I. Protein kinetics during and after long‐term spaceflight on MIR. Am J Physiol 276: E1014‐E1021, 1999.
 502.Stephenson GM. Hybrid skeletal muscle fibres: A rare or common phenomenon ? Clin Exp Pharmacol Physiol 28: 692‐670, 2001.
 503.Stienen GJM, Kiers J, Bottinelli R, Reggiani C. Myofibrillar ATPase activity in skinned human skeletal muscle fibres: fibre type and temperature dependence. J Physiol 493: 299‐307, 1996.
 504.Storey KB, Storey JM. Metabolic rate depression in animals: Transcriptional and translational controls. Biol Rev Camb Philos Soc 79: 207‐233, 2004.
 505.Stromer MH, Goll DE. Studies on purified ‐actinin. II. Electron microscopic studies on the competitive binding of ‐actinin and tropomyosin to Z‐line extracted myofibrils. J Mol Biol 67: 489‐494, 1972.
 506.Suzuki N, Motohashi N, Uezumi A, Fukada S, Yoshimura T, Itoyama Y, Aoki M, Miyagoe‐Suzuki Y, Takeda S. NO production results in suspension‐induced muscle atrophy through dislocation of neuronal NOS. J Clin Invest 117: 2468‐2476, 2007.
 507.Tang D, Mehta D, Gunst SJ. Mechanosensitive tyrosine phosphorylation of paxillin and focal adhesion kinase in tracheal smooth muscle. Am J Physiol 276: C250‐C258, 1999.
 508.Tanner CJ, Barakat HA, Dohm GL, Pories WJ, MacDonald KG, Cunningham PR, Swanson MS, Houmard JA. Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab 282: E1191‐E1196, 2002.
 509.Termin A, Staron RS, Pette D. Changes in myosin heavy chain isoforms during chronic low‐frequency stimulation of rat fast hindlimb muscles. A single‐fiber study. Eur J Biochem 186: 749‐754, 1989a.
 510.Termin A, Staron RS, Pette D. Myosin heavy chain isoforms in histochemically defined fiber types of rat muscle. Histochemistry 92: 453‐457, 1989b.
 511.Thomason D, Booth F. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol 68: 1‐12, 1990.
 512.Timson BF, Bowlin BK, Dudenhoeffer GA, George JB. Fiber number, area, and composition of mouse soleus muscle following enlargement. J Appl Physiol 58: 619‐624, 1985.
 513.Tinker DB, Harlow HJ, Beck TD. Protein use and muscle‐fiber changes in free‐ranging, hibernating black bears. Physiol Zool 71: 414‐424, 1998.
 514.Tobin C, Joubert Y. Testosterone‐induced development of the rat levator ani muscle. Dev Biol 146: 131‐138, 1991.
 515.Tomas FM, Munro HN, Young VR. Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of N tau‐methylhistidine. Biochemical J 178: 139‐146, 1979.
 516.Toniolo L, Maccatrozzo L, Patruno M, Pavan E, Caliaro F, Rossi R, Rinaldi C, Canepari M, Reggiani C, Mascarello F. Fiber types in canine muscles: Myosin isoform expression and functional characterization. Am J Physiol Cell Physiol 292: C1915‐C1926, 2007.
 517.Tothova J, Blaauw B, Pallafacchina G, Rudolf R, Argentini C, Reggiani C, Schiaffino S. NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle. J Cell Sci 119: 1604‐1611, 2006.
 518.Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P. Human single muscle fibre function with 84 day bed‐rest and resistance exercise. J Physiol 557: 501‐513, 2004.
 519.Tsika RW, Herrick RE, Baldwin KM. Time course adaptations in rat skeletal muscle isomyosins during compensatory growth and regression. J Appl Physiol 63: 2111‐2121, 1987.
 520.Tsukiyama‐Kohara K, Poulin F, Kohara M, DeMaria CT, Cheng A, Wu Z, Gingras AC, Katsume A, Elchebly M, Spiegelman BM, Harper ME, Tremblay ML, Sonenberg N. Adipose tissue reduction in mice lacking the translational inhibitor 4E‐BP1. Nat Med 7: 1128‐1132, 2001.
 521.Turner DL, Jones DA, McIntyre DB, Newham DJ. ATP turnover measured by 31P‐magnetic resonance spectroscopy in human adductor pollicis during isometric and shortening contractions. J Physiol 459: 154P, 1993.
 522.Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age‐ and diet‐induced obesity while enhancing insulin sensitivity. Nature 431: 200‐205, 2004.
 523.Urso M, Clarkson P. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189: 41‐54, 2003.
 524.van der Linden G, Simonides W, van Hardeveld C. Thyroid hormone regulates Ca2þ‐ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle. Mol Cell Endocrinol 90: 125‐131, 1992.
 525.Van Deveire KN, Scranton SK, Kostek MA, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Thompson PD, Devaney JM, Gordish‐Dressman H, Hoffman EP, Maresh CM, Pescatello LS. Variants of the ankyrin repeat domain 6 gene (ANKRD6) and muscle and physical activity phenotypes among European‐derived American adults. J Strength Cond Res 26: 1740‐1748, 2012.
 526.van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid‐mediated diabetogenic effects: Towards expansion of therapeutic options? Eur J Clin Invest 39: 81‐93, 2009.
 527.van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ, Jr., Olson EN. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17: 662‐673, 2009.
 528.Vavvas D, Apazidis A, Saha AK, Gamble J, Patel A, Kemp BE, Witters LA, Ruderman NB. Contraction‐induced changes in acetyl‐CoA carboxylase and 5'‐AMP‐activated kinase in skeletal muscle. J Biol Chem 272: 13255‐13261, 1997.
 529.Velickovska V, Lloyd BP, Qureshi S, van Breukelen F. Proteolysis is depressed during torpor in hibernators at the level of the 20S core protease. J Comp Physiol [B] 175: 329‐335, 2005.
 530.Vella L, Caldow MK, Larsen AE, Tassoni D, Della Gatta PA, Gran P, Russell AP, Cameron‐Smith D. Resistance exercise increases NF‐kappaB activity in human skeletal muscle. Am J Physiol Regulatory Integr Comp Physiol 302: R667‐R673, 2012.
 531.Vescovo G, Ambrosio GB, Dalla Libera L. Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure. Acta Physiol Scand 171: 305‐210, 2001.
 532.Vingren JL, Kraemer WJ, Ratamess NA, Anderson JM, Volek JS, Maresh CM. Testosterone physiology in resistance exercise and training: The up‐stream regulatory elements. Sports Med 40: 1037‐1053, 2010.
 533.Vogt M, Hoppeler H. Is hypoxia training good for muscles and exercise performance? Prog Cardiovasc Dis 52: 525‐533, 2010.
 534.Wada S, Kato Y, Okutsu M, Miyaki S, Suzuki K, Yan Z, Schiaffino S, Asahara H, Ushida T, Akimoto T. Translational suppression of atrophic regulators by microRNA‐23a integrates resistance to skeletal muscle atrophy. J Biol Chem 286: 38456‐38465, 2011.
 535.Wagner P. The critical role of VEGF in skeletal muscle angiogenesis and blood flow. Biochem Soc Trans 39: 1556‐1159, 2011.
 536.Wahl P, Bloch W, Schmidt A. Exercise has a positive effect on endothelial progenitor cells, which could be necessary for vascular adaptation processes. Int J Sports Med 28: 374‐380, 2007.
 537.Walker DK, Dickinson JM, Timmerman KL, Drummond MJ, Reidy PT, Fry CS, Gundermann DM, Rasmussen BB. Exercise, amino acids, and aging in the control of human muscle protein synthesis. Med Sci Sports Exerc 43: 2249‐2258, 2011.
 538.Walker DK, Fry CS, Drummond MJ, Dickinson JM, Timmerman KL, Gundermann DM, Jennings K, Volpi E, Rasmussen BB. PAX7+ satellite cells in young and older adults following resistance exercise. Muscle Nerve 46: 51‐59, 2012.
 539.Wang RC, Wei Y, An Z, Zou Z, Xiao G, Bhagat G, White M, Reichelt J, Levine B. Akt‐mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science 338: 956‐959, 2012.
 540.Weill L, Belloc E, Bava FA, Mendez R. Translational control by changes in poly(A) tail length: Recycling mRNAs. Nat Struct Mol Biol 19: 577‐585, 2012.
 541.Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO, Kelly DP. A role for the transcriptional coactivator PGC‐1alpha in muscle refueling. J Biol Chem 282: 36642‐36651, 2007.
 542.White RB, Bierinx AS, Gnocchi VF, Zammit PS. Dynamics of muscle fibre growth during postnatal mouse development. BMC Dev Biol 10: 21, 2010.
 543.Whyte J, Laughlin M. The effects of acute and chronic exercise on the vasculature. Acta Physiol 199: 441‐450, 2010.
 544.Wicks K, Hood D. Mitochondrial adaptations in denervated muscle: Relationship to muscle performance. Am J Physiol Cell Physiol 260: C841‐C850, 1991.
 545.Widrick J, Stelzer J, Shoepe T, Garner D. Functional properties of human muscle fibers after short‐term resistance exercise training. Am J Physiol Regul Integr Comp Physiol 283: R408‐R416, 2002.
 546.Widrick JJ, Knuth ST, Norenberg KM, Romatowski JG, Bain JL, Riley DA, Karhanek M, Trappe SW, Trappe TA, Costill DL, Fitts RH. Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J Physiol 516: 915‐930, 1999.
 547.Widrick JJ, Maddalozzo GF, Hu H, Herron JC, Iwaniec UT, Turner RT. Detrimental effects of re‐loading recovery on force, shortening velocity, and power of soleus muscles from hindlimb unloaded rats. Am J Physiol Regul Integr Comp Physiol 2008.
 548.Widrick JJ, Romatowski JG, Bain JL, Trappe SW, Trappe TA, Thompson JL, Costill DL, Riley DA, Fitts RH. Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers. Am J Physiol 273: C1690‐C1699, 1997.
 549.Willmott A, White C, Deukelov S. Fibrillation potential onset in peripheral nerve injury. Muscle Nerve 46: 332‐340, 2012.
 550.Winbanks CE, Weeks KL, Thomson RE, Sepulveda PV, Beyer C, Qian H, Chen JL, Allen JM, Lancaster GI, Febbraio MA, Harrison CA, McMullen JR, Chamberlain JS, Gregorevic P. Follistatin‐mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol 197: 997‐1008, 2012.
 551.Windisch A, Gundersen K, Szabolcs MJ, Gruber H, Lomo T. Fast to slow transformation of denervated and electrically stimulated rat muscle. J Physiol 510: 623‐632, 1998.
 552.Witzemann V, Brenner H, Sakmann B. Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses. J Cell Biol 114: 125‐141, 1991.
 553.Wu H, Naya FJ, McKinsey TA, Mercer B, Shelton JM, Chin ER, Simard AR, Michel RN, Bassel‐Duby R, Olson EN, Williams RS. MEF2 responds to multiple calcium‐regulated signals in the control of skeletal muscle fiber type. EMBO J 19: 1963‐1973, 2000.
 554.Wu Y, Baker M, Crumley R, Caiozzo V. Single‐fiber myosin heavy‐chain isoform composition of rodent laryngeal muscle: Modulation by thyroid hormone. Arch Otolaryngol Head Neck Surg 126: 874‐880, 2000.
 555.Wu Y, Baker M, Marie J, Crumley RL, Caiozzo V. The plasticity of denervated and reinnervated laryngeal muscle: Focus on single‐fiber myosin heavy‐chain isoform expression. Arch Otolaryngol Head Neck Surg 130: 1070‐1082, 2004.
 556.Wyss‐Dunant E. The mountain world (English version edited by Malcolm Barnes). 1960.
 557.Xu R, Andres‐Mateos E, Mejias R, Macdonald E, Leinwand L, Merriman D, Fink R, Cohn R. Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization. Exp Neurol (in press), 2013.
 558.Yang S, Alnaqeeb M, Simpson H, Goldspink G. Cloning and characterization of an IGF‐1 isoform expressed in skeletal muscle subjected to stretch. J Muscle Res Cell Motil 17: 487‐495, 1996.
 559.You JS, Frey JW, Hornberger TA. Mechanical stimulation induces mTOR signaling via an ERK‐independent mechanism: Implications for a direct activation of mTOR by phosphatidic acid. PLoS One 7: e47258, 2012.
 560.Zanchi N, de Siqueira FM, Lira F, Rosa J, Yamashita A, de Oliveira Carvalho CR, Seelaender M, Lancha AJ. Chronic resistance training decreases MuRF‐1 and Atrogin‐1 gene expression but does not modify Akt, GSK‐3beta and p70S6K levels in rats. Eur J Appl Physiol 106: 415‐423, 2009.
 561.Zeman RJ, Ludemann R, Easton TG, Etlinger JD. Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta2‐receptor agonist. Am J Physiol Endocrinol Metab 254: E726‐E732, 1988.
 562.Zhang QJ, Li QX, Zhang HF, Zhang KR, Guo WY, Wang HC, Zhou Z, Cheng HP, Ren J, Gao F. Swim training sensitizes myocardial response to insulin: Role of Akt‐dependent eNOS activation. Cardiovasc Res 75: 369‐380, 2007.
 563.Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, Lecker SH, Goldberg AL. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6: 472‐483, 2007.
 564.Zhong H, Roy RR, Woo J, Kim JA, Edgerton VR. Differential modulation of myosin heavy chain phenotype in an inactive extensor and flexor muscle of adult rats. J Anat 210: 19‐31, 2007.
 565.Zhou Y, Liu D, Kaminski H. Myosin heavy chain expression in mouse extraocular muscle: More complex than expected. Invest Ophthalmol Vis Sci 51: 6355‐6363, 2010.
 566.Zierath J. Exercise training‐induced changes in insulin signaling in skeletal muscle. J Appl Physiol 93: 773‐781, 2002.
 567.Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ. Induction of cachexia in mice by systemically administered myostatin. Science 296: 1486‐1488, 2002.
 568.Zorzato F, Volpe P, Damiani E, Quaglino D, Jr., Margreth A. Terminal cisternae of denervated rabbit skeletal muscle: Alterations of functional properties of Ca2+ release channels. Am J Physiol 257: C504‐C511, 1989.
 569.Zumstein A, Mathieu O, Howald H, Hoppeler H. Morphometric analysis of the capillary supply in skeletal muscles of trained and untrained subjects–its limitations in muscle biopsies. Pflugers Arch 397: 277‐283, 1983.
 570.Zuo L, Christofi FL, Wright VP, Bao S, Clanton TL. Lipoxygenase‐dependent superoxide release in skeletal muscle. J Appl Physiol 97: 661‐668, 2004.
 571.Zwetsloot KA, Westerkamp LM, Holmes BF, Gavin TP. AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise. J Physiol 586: 6021‐6035, 2008.

Related Articles:

Muscle Plasticity: Energy Demand and Supply Processes
Molecular Mechanisms of Muscle Plasticity with Exercise
Lack of Exercise Is a Major Cause of Chronic Diseases

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Bert Blaauw, Stefano Schiaffino, Carlo Reggiani. Mechanisms Modulating Skeletal Muscle Phenotype. Compr Physiol 2013, 3: 1645-1687. doi: 10.1002/cphy.c130009