Comprehensive Physiology Wiley Online Library

Ultrastructure of the Heart

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Abstract

The sections in this article are:

1 Shape, Motion, and Force Vectors
2 The Extracellular Matrix
2.1 Collagen Weave
2.2 Transverse (T)‐Tubules
3 Interior Supporting Networks
3.1 Microtubules
3.2 Intermediate Filament Network
3.3 Sarcolemmal Associations
3.4 Titin Filament Network
4 The Myofilament Bundles and Associated Structures
5 The Dynamic Z‐Band Lattice
5.1 Contractile and Elastic Components in Relation to the Z‐Band
5.2 Protein Composition
5.3 Perturbed States of the Z‐Band
5.4 Functional States of the Z‐Band
6 Summary
Figure 1. Figure 1.

Regularly repeating array of myofibrils and mitochondria in two cells and portions of two intercalated disks of dog papillary muscle fixed at rest length by immersion in glutaraldehyde–formaldehyde and postfixed with osmium tetroxide.

Figure 2. Figure 2.

Portions of two cardiac cells showing mitochondria (Mi) and stair step configurations of intercalated disks (ID) in longitudinal sections of dog papillary muscle.

Figure 3. Figure 3.

Longitudinal section of a normal dog papillary muscle cell reveals most of the repeating sarcomere structures. Thick and thin filaments exhibit typical banding pattern (A, I, Z, M). Large mitochondria with tightly packed cristae are found along and between the usually large myofilament bundles. Microtubules (Mt), glycogen (G) and profiles of sarcoplasmic reticulum (SR) are visible in the planes between myofibrils. T‐tubules (T) and terminal sacs of sarcoplasmic reticulum form triads. Intermediate filaments (IF) oriented transverse to the myofibril axis are visible near T‐tubules. Note portion of mitochondrion tracking along the microtubule (arrow) 98.

Reprinted by permission of Rockefeller University Press
Figure 4. Figure 4.

Artist's sketch of cardiac muscle showing cut‐away three‐dimensional view of several sarcomeres. A = A‐band; I = I‐band; ID = intercalated disc 98.

Reprinted by permission of Rockefeller University Press
Figure 5. Figure 5.

Guinea pig papillary muscle in thin longitudinal section. Microtubules (arrows), intermediate filaments and sarcoplasmic reticulum (SR) profiles are visible around the myofilament bundles and the fenestrated collar (FC) of the SR.

Figure 6. Figure 6.

Longitudinal section of normal dog cardiac muscle cell. Thick and thin filaments of A‐band hexagonal lattice are shown in two different orientations (A) with respect to this longitudinal plane of section through the middle of a myofibril. Mitochondrial profiles appear flattened in this view (refer to diagram in Figure 4). Note variation in Z‐width (arrows) and the change in orientation of Z‐lattice with respect to the plane of section.

Figure 7. Figure 7.

Interstitial area between rabbit myocytes, ultrarapidly frozen, freeze‐fractured, and then etched. The banded collagen fibrils are abundant and fill the interstitial space. With etching, the microthread network is evident as an extensive weave connecting collagen fibril to fibril 347.

Reprinted by permission of Academic Press
Figure 8. Figure 8.

High‐magnification micrograph of deep‐etched replica showing the collagen fibril microthread meshwork. The intertangled network that bridges and wraps around the collagen fibrils is visible in three‐dimensional array. Granules of ∼8–10 nm diameter are apparent at branch points of the microfibril‐microthread lattice (arrow) 347.

Reprinted by permission of Academic Press
Figure 9. Figure 9.

Freeze‐fractured, deep‐etched replica from unfixed ultrarapidly frozen rabbit heart exposed to 0‐Ca perfusion. The external lamina (el) is seen pulled back from the surface of the myocyte sarcolemma. The attachment of the external lamina is maintained at several sites by trabeculae (arrows). The demarcation between the bilayer surface of the cell and the fractured P face of the membrane is clearly visible (arrowhead) 347.

Reprinted by permission of Academic Press
Figure 10. Figure 10.

Freeze‐fractured, deep‐etched replica from unfixed ultrarapidly frozen rabbit heart exposed to 0‐Ca perfusion. This lower magnification micrograph should be compared to Figure 10. As in that figure, the external lamina (el) is pulled away from the sarcolemma but attached by trabeculae (arrows). Arrowhead indicates the demarcation between the bilayer cell surface and the fractured P face of the membrane 347.

Reprinted by permission of Academic Press
Figure 11. Figure 11.

Freeze‐etch micrograph of unfixed ultrarapidly frozen rabbit papillary muscle. At this magnification, the connecting matrix of fine fibrils in between and connecting the collagen and the muscle surface is visible (arrows). In addition to the collagen bundle fibrils, individual 54 nm diameter collagen fibrils are visible at the myocyte cell surface (myo) 75.

Reprinted by permission of S. Karger
Figure 12. Figure 12.

Another view of unfixed ultrarapidly frozen rabbit papillary muscle. The regularly arranged trabeculae of the external lamina of the myocyte appear to insert directly into the bilayer. The series of linkages from collagen to myocyte membrane is visible. External lamina trabeculae of ‘posts’ (arrow) insert or attach to the bilayer. A fine line marks the boundary between the outer surface and the P face of the bilayer (arrowheads) 75.

Reprinted by permission of S. Karger
Figure 13. Figure 13.

Freeze‐etch electron micrograph of 4 day‐old rat myocyte. This high‐magnification micrograph shows that by 4 days the cell surface and extracellular matrix fibrils are similar in density and organization to the adult. The trabeculae that link the external lamina into the bilayer are clearly visible (arrows) 75.

Reprinted by permission of S. Karger
Figure 14. Figure 14.

Conventionally prepared (2% tannic acid present) thin‐section electron micrograph shows the interstitial space between a rabbit myocyte (MYO) on the left and a capillary (CAP) on the right. The collagen fibrils run parallel to the long axis of the myocyte, with some collagen fibrils branching laterally to link with the myocyte cell surface and, on the other side, to the capillary. The individual structures involved in the linkages are not clearly visible in this type of preparation 75.

Reprinted by permission of S. Karger
Figure 15. Figure 15.

High‐magnification freeze‐etch micrograph depicting collagen fibrils from adult rat heart. Compare to neonatal material shown in Figure 16 75.

Reprinted by permission of S. Karger
Figure 16. Figure 16.

High‐magnification freeze‐etch micrograph depicting collagen fibrils from 4 day‐old neonatal rat heart. The collagen fibrils and the extensive connections linking them, microthreads, microfibrils, and granules, appear similar to that in the adult shown in Figure 15 75.

Reprinted by permission of S. Karger
Figure 17. Figure 17.

Grazing profiles of cell membrane (intercalated disk = ID, calveolae = arrows) of dog papillary muscle showing relation of extracellular components (collagen = Co) to intracellular features (mitochondria = Mi) at the cell surface.

Figure 18. Figure 18.

Cross section of dog papillary muscle showing cross‐cut collagen (Co) within extracellular matrix. Appearance of clear spaces is due to extraction during chemical fixation and an artifact of preparation. Note tufts of dense material just beneath the sarcolemma in cell at level of Z‐bands (arrows).

Figure 19. Figure 19.

Longitudinal section of dog papillary muscle showing cross‐cut profiles of T‐tubules (T) with lumen contents the same density as the extracellular matrix (collagen = Co) at the cell surface.

Figure 20. Figure 20.

Sarcolemma and T‐tubule (T) at cell surface is shown in longitudinal section of dog papillary muscle. Note varying shape of large mitochondrion (Mi) with microtubule (Mt) spanning the myofibril surface at an angle. T‐tubule lumen contains extracellular matrix material. The grazing cut of the large T‐tubule membrane shows the sarcoplasmic reticulum (SR) and intermediate filaments (IF) overlying a Z‐band not visible in this very thin section. Profiles of myofilaments show that the plane of section is not exactly longitudinal with respect to the lattice plane of the hexagonal arrangement of thick and thin filaments.

Figure 21. Figure 21.

A longitudinal section at same magnification as in Figure 20 shows fibroblast enmeshed in extracellular matrix. Indentations of the sarcolemma of this muscle cell indicate T‐tubules (T), but the section plane is not through the middle of the tubule to show the full extent of the lumen.

Figure 22. Figure 22.

A longitudinal section of dog papillary muscle at higher magnification than Figures 20 and 21 partly through the middle of the T‐tubule (T) shows invagination of the sarcolemma, the extracellular matrix material, the diads and triads (arrows) formed with adjacent sarcoplasmic reticulum (SR), the outpocketing of the T‐tubule membrane, a bristle‐coated vesicle emerging (arrowhead) and the subjacent SR and intermediate filaments (IF). Note the good alignment with the Z‐bands in the adjacent myofilament bundle and how the mitochondria conform to the space between adjacent T‐tubules.

Figure 23. Figure 23.

Cross section of guinea pig papillary muscle showing cross‐cut microtubules (arrows) distributed around the surface of the nucleus as well as between myofilament bundles.

Figure 24. Figure 24.

Longitudinal section of guinea pig papillary muscle showing longitudinal profiles of microtubules (arrows) near the nucleus.

Figure 25. Figure 25.

Cross section of rat papillary muscle showing microtubules around the nucleus (arrows). This muscle has been stretched in a relaxing solution. Note how many microtubules 27 can be seen when they are aligned perpendicular to the plane of section.

Figure 26. Figure 26.

Longitudinal section of contracted dog papillary muscle showing longitudinal profiles of microtubules (arrows) coming in and out of the plane of section near convoluted nucleus 98.

Reprinted by permission of Rockefeller University Press
Figure 27. Figure 27.

Cross section of dog papillary muscle at level of Z‐band showing cross‐sectional profiles of microtubules (arrows), longitudinal profiles of intermediate filaments (IF), sarcoplasmic reticulum (SR) adhering to myofilament bundles with specialized regions of SR forming a complex with the T‐tubule (arrowheads), and glycogen.

Figure 28. Figure 28.

Cross‐sectional profiles of microtubules (arrows) in rat papillary muscle at higher magnification showing their location next to mitochondria (Mi) and just outside the profiles of the Sarcoplasmic reticulum at the level of the Z‐bands and at the A–I junction.

Figure 29. Figure 29.

Cross section of dog papillary myofilament bundles at the level of the A‐band showing microtubule profiles (arrows) near mitochondria. The microtubules and membranes of the mitochondria are enhanced by treatment of muscle with 8% tannic acid before post‐fixation with osmium tetroxide.

Figure 30. Figure 30.

Longitudinal section of dog papillary muscle showing microtubules (arrows) at cell surface. Three T‐tubule profiles are evident (T). Microtubules arch across the surface of the myofilament bundles. Note also varying shapes of mitochondrial profiles. Portion of fibroblast is visible between two cells.

Figure 31. Figure 31.

Structure of myocardial cells at the level of light and electron microscopy is portrayed. Top: A portion of ventricular myocardium with branching muscle cells enmeshed in collagen. Nuclei are centrally placed and intercalated disks contain sites for end‐to‐end attachment of cells. Middle: Ultrastructure of portions of two cells in a cutaway view displaying the arrangement of myofibrils. A network of intermediate filaments, which surrounds the myofibrils like a cage, is periodically anchored to cell membrane plaques at the Z‐bands and at transverse regions of the intercalated disks. Bottom: Within the sarcomeres, the contractile units of the muscle delimited at each end by a Z‐band consist of three sets of filaments. Thick filaments containing primarily myosin are located in the A‐band; thin filaments containing actin, tropomyosin, and troponin, and thin elastic filaments of titin extend from each Z‐band toward the middle of the sarcomere. The thick and thin filaments interdigitate regularly to form a hexagonal array seen in cross section. The titin filaments attach periodically along the thick filament. The Z‐band is a lattice of axial and cross‐connecting Z‐filaments. In the Z‐band, the ends of the thin filaments from adjacent sarcomeres overlap and interdigitate in a centered tetragonal array and are held together periodically by cross‐connecting Z‐filaments 104.

Reprinted by permission of the American Physiological Society
Figure 32. Figure 32.

Cross section of cat papillary muscle showing longitudinal profile of intermediate filaments (IF) near Z‐bands and intercalated disk (ID). Long profile of T‐tubule with portions of two diads (one at each end, arrows) near the intercalated disk (see diagram in Figure 4 for orientation). Note gap junction at lower right (arrowhead).

Figure 33. Figure 33.

Longitudinal section of dog papillary muscle showing intermediate filament bundles (IF) near cell surface at desmosome‐like regions extending across the surface of the myofilaments at the Z band level and intermediate filament bundles at three other Z‐bands.

Figure 34. Figure 34.

Longitudinal section of dog papillary muscle showing intermediate filament bundles (IF) at three different Z‐band levels spanning several myofilament bundles. Note profiles of sarcoplasmic reticulum (SR) and microtubules (arrows).

Figure 35. Figure 35.

Longitudinal section of dog papillary muscle showing intermediate filaments and microtubules.

Figure 36. Figure 36.

Cross section of rat papillary muscle showing mitochondria and myofilament bundles, the two most prominent features of the cardiac sarcomere, together with two cytoskeletal components—cross‐cut profiles of microtubules (Mt) and longitudinal profiles of intermediate filaments (IF). Note caveolae of sarcolemma of adjacent cell (arrows).

Figure 37. Figure 37.

Cross section of rat papillary muscle in interior of cell showing hexagonal arrangement of thick and thin contractile filaments in M‐band and A‐band. A T‐tubule profile (T) at the level of the Z‐band shows the region of contact with the sarcoplasmic reticulum specialized for excitation–contraction coupling and the “feet” structures (arrowheads).

Figure 38. Figure 38.

Longitudinal section of dog papillary muscle showing long mitochondrial profile (Mi) spanning three sarcomeres. Note bowing profile of microtubule (arrow) aligning with surfaces of three different mitochondrial profiles and the partially extracted lipid droplet (Li) between two mitochondrial profiles.

Figure 39. Figure 39.

Longitudinal section of dog papillary muscle showing relationship between varying shapes of mitochondrial profiles (Mi) and the intermediate filament (IF) bundles that maintain registration between adjacent Z‐bands perpendicular to the myofibril axis. Note that the myofilament bundles are not aligned exactly in the longitudinal plane of section.

Figure 40. Figure 40.

Longitudinal section of dog papillary muscle showing the relationship between longitudinal profiles of microtubules (arrows), sarcoplasmic reticulum, T‐tubules (T), intermediate filaments (IF) and adjacent myofilament bundles 98.

Reprinted by permission of Rockefeller University Press
Figure 41. Figure 41.

Cross section of myofilament bundles from papillary muscle showing A, I and Z‐bands. Compare with Figure 6 to see corresponding appearance in a longitudinal section of papillary muscle.

Figure 42. Figure 42.

Cross section of rat papillary myofilament bundle at level of Z‐band showing one of the unusual myofibril shapes.

Figure 43. Figure 43.

Thin longitudinal section of dog papillary myofibril. Periodicities along thick and thin filaments can be seen by viewing figure from above at 45 degrees. Striations within M‐band and Z‐lattices can be seen at this magnification. Note N‐lines (arrowheads).

Figure 44. Figure 44.

Thick and thin filaments in hexagonal array in cross section of A‐band can be seen by viewing the figure from above at 45 degrees. Try rotating the figure as you view to get best perspective.

Figure 45. Figure 45.

Cross section of dog papillary myofibril at level of M‐band and edge of A‐band. Note distinct triangular appearance of cross‐cut thick filaments and the filaments connecting all six thick filaments and a central thick filament in several arrays in middle of M‐band. Some thin filaments penetrate into the H‐zone because some are much longer than others.

Figure 46. Figure 46.

Cross section of sarcomere near nucleus exhibits M‐band ordering of thick filaments. Adjacent myofilament bundles are at I‐band level. Not all myofibrils are in exact register across the cell in cardiac muscle.

Figure 47. Figure 47.

Thin filaments in I‐band lack precise symmetry, are not random, but exhibit nearest‐neighbor ordering. Note connections between some pairs of thin filaments in this cross section of dog papillary muscle.

Figure 48. Figure 48.

Cross section of Z‐band lattice of a single sarcomere. The basket weave, or bw, lattice appearance predominates in this unstimulated cardiac muscle.

Figure 49. Figure 49.

Cross section of unstimulated dog papillary muscle showing portion of Z‐band exhibiting two different lattice appearances: the basket weave pattern (bw) predominates, but a small region of small square pattern (ss) is visible at far right.

Figure 50. Figure 50.

Longitudinal section of Z‐band anchored near the sarcolemma. The chevron pattern typical of this 24 nm (1,0) orientation of the Z‐lattice is shown. Thin filaments of adjacent sarcomeres interdigitate and the distance between adjacent thin filaments from the same sarcomere is 24 nm.

Figure 51. Figure 51.

Longitudinal section of Z‐band showing intermediate filaments (IF) going between adjacent Z‐bands and around periphery of Z‐lattice.

Figure 52. Figure 52.

Longitudinal section of Z‐band lattice exhibiting chevron appearance typical of the 24 nm (1,0) orientation. This Z lattice is especially uniform with respect to the plane of section, yet there are 3–4 subunits visible at the left, whereas at the bottom only two are visible. This is seen most easily if viewed at an angle of 45 degrees.

Figure 53. Figure 53.

Longitudinal section of Z‐band in same orientation as Figure 52, but the sarcomere is longer. The appearance of the Z‐lattice is the same. Experimental evidence shows that passive stretch does not induce a change in lattice appearance or spacing. Intermediate filaments (IF) are visible between adjacent Z‐bands.

Figure 54. Figure 54.

Longitudinal section of Z‐band in 17 nm 1 orientation (17 is half‐diagonal of a 24 nm square). Thin filaments appear to go straight through the Z‐band, when in fact the overlapping ends of the thin filaments form a centered square arrangement.

Figure 55. Figure 55.

Longitudinal section from human atrial biopsy showing widening of several Z‐bands. Note loss of exact registration of thick and thin filaments within the sarcomeres. Edges of I, A, and M‐bands are uneven.

Figure 56. Figure 56.

Longitudinal section of normal dog cardiac sarcomeres showing Z‐bands of different widths. The Z‐band at the bottom left has the usual appearance, is well centered in the I‐band, and the M‐bands of adjacent sarcomeres are in register. The widened Z‐band in the next sarcomere of the same myofilament bundle is taking up more of the I‐band. The two widest Z‐bands flanking a barrel‐shaped A‐band take up most of the I‐band.

Figure 57. Figure 57.

Longitudinal section of papillary muscle taken from another normal dog showing the profile of Z‐band material spanning the entire sarcomere length and maintaining continuity with adjacent sarcomeres both in the same myofilament bundle and in the adjacent myofilament bundle.

Figure 58. Figure 58.

Z‐crystals in aged cat myocardium in several different orientations with respect to plane of section. All are aligned along the myofibril axis and all have thin filaments emerging into normal‐looking A‐bands with normal Z‐bands at the opposite ends of these sarcomeres.

Figure 59. Figure 59.

Longitudinal section of Z‐crystal or rod in normal dog papillary muscle. Note continuity of axial filaments with thin filaments in the adjacent I‐band and chevron pattern of normal Z‐band. The three‐dimensional reconstructions of Z‐rod and normal Z‐band are very similar.

Figure 60. Figure 60.

Typical sarcomere seen in normal myofibers adjacent to dog heart cell containing Z‐crystal shown in Figure 59. The A‐band length is 1.56 μm. The 17 nm 1 orientation of the Z‐band (arrowhead) where the thin filaments appear to pass through the Z‐band lattice is one of the two orientations of the tetragonal Z‐lattice that gives maximal reinforcement to the axial filaments.

Figure 61. Figure 61.

High‐voltage electron micrograph of half‐micron section of dog cardiac muscle. The exact alignment of thick and thin filaments within each sarcomere gives reinforcement of the banding patterns, Z, I, A, M, but registration of adjacent myofilament bundles is not exact. Compare to high‐magnification cross sections of thin sections of myofilaments shown in Figures 37,41, and 46. Note the abundance of glycogen granules (G) in these thick sections.

Figure 62. Figure 62.

High‐voltage electron micrograph of half‐micron section of cardiac muscle. Note the variation in Z‐band width (i.e. number of lattice subunits in axial direction) occurring within a region of the same lattice orientation (arrows) and occurring in a region of changing orientation toward the top of the figure. The periodicities within the I, A, and M‐bands are clearly visible. The glycogen granules (G) appear as black dots, mostly in I‐band but also one or two in M‐band.

Figure 63. Figure 63.

Electron micrograph of unstimulated cardiac muscle in cross section showing the Z‐band in the bw form and the adjacent A‐bands.

Figure 64. Figure 64.

Electron micrograph of a cross section of soleus perfusion‐fixed during a tetanic contraction in situ. The bw form of the Z‐lattice is predominant 103.

Reprinted by permission of Kluwer Academic and Lippencott‐Raven Publishers
Figure 65. Figure 65.

Electron micrograph of a cross section of rat soleus muscle stretched in a muscle myograph in 100 mM PIPES buffer by applying a load of 3 g, adjusting for stress relaxation and fixing at the final length achieved after 30 min at 3 g load. The Z‐lattice exhibits the small square (ss) pattern.

Figure 66. Figure 66.

Cross section of rat soleus muscle stretched in a muscle myograph in 100 mM PIPES buffer by applying a load of 6 g, adjusting for stress relaxation, and fixing at the final length achieved after 30 min at 6 g load. The average sarcomere length of this muscle preparation was 2.5 μm. The Z‐band exhibits the small square (ss) lattice pattern.

Figure 67. Figure 67.

Longitudinal section of adult rat soleus muscle stretched by a 6 g load in a bath containing 5 mM EGTA in 100 mM PIPES buffer, pH 7.2. At least five distinct stripes (arrowheads) are present in the I‐band on either side of the Z‐band, four of which are within a region of increased electron density as well as the N2 line (arrow). Sarcomere lengths in this section average 3.35. Section is 200 nm thick, stained with uranyl acetate and Sato's lead stain, and photographed at 200 kV.

Figure 68. Figure 68.

Cross section of rat papillary muscle stretched in a bath containing 5 mM EGTA in 100 mM PIPES buffer, pH 7.2. Note the uniform small square (ss) appearance of the cardiac Z‐band in relaxed muscle. Empty T‐tubules and dark granules in mitochondria are both signs of altered calcium distribution in the cell due to chelation of calcium by EGTA.

Figure 69. Figure 69.

Electron micrograph of EGTA treated cardiac muscle in cross section showing the Z‐band in the ss form 102.

Reprinted by permission of the American Physiological Society
Figure 70. Figure 70.

A projection of a 25 nm‐thick longitudinal section taken from a three‐dimensional reconstruction of the Z‐band from unstimulated skeletal muscle. Axial filaments enter the Z‐band from top and bottom of the figure (arrowheads). Crossconnecting Z‐filaments appear to connect the axial filaments in this “chevron” (1,0) orientation projection (scale bar = 10nm) 276.

Reprinted by permission of Rockefeller University Press
Figure 71. Figure 71.

A stereo‐shaded solid rendering of the three‐dimensional reconstruction of Plate 1. Compare to Figures 72 and 74; scale bar = 10 nm.

Figure 72. Figure 72.

Stereo‐shaded solid rendering of a longitudinal section from a three‐dimensional reconstruction of rigor skeletal muscle. Axial filaments enter from the top and bottom of the figure and are interconnected at the edges of the Z‐band by an array of cross‐connecting Z‐filaments. There appear to be fewer crossconnections in this rigor Z‐band than in the unstimulated muscle shown in Plate 1 and Figures 70 and 71. The vertical spacing between crossconnections is larger than in the unstimulated muscle; scale bar = 10 nm.

Figure 73. Figure 73.

Projection of a 20 nm longitudinal slice from a preliminary three‐dimensional reconstruction of unstimulated cardiac Z‐band. Compare similar projection view of longitudinal slice from three‐dimensional reconstruction of unstimulated skeletal muscle sseen in Figure 70; scale bar = 10 nm.

Figure 74. Figure 74.

Grey‐scale shaded solid stereo pair of a portion of a three‐dimensional reconstruction of the Z‐band lattice in unstimulated rat cardiac muscle, shown in a longitudinal orientation. This muscle exhibits the basket weave form of the lattice in cross section. Thin axial filaments enter the Z‐band from the top and bottom the figure, where they are interconnected by an array of Z‐band cross‐connecting filaments. In this view, the cross‐connecting filaments attach at intervals of ∼20 nm along the axial filament; scale bar = 10 nm.



Figure 1.

Regularly repeating array of myofibrils and mitochondria in two cells and portions of two intercalated disks of dog papillary muscle fixed at rest length by immersion in glutaraldehyde–formaldehyde and postfixed with osmium tetroxide.



Figure 2.

Portions of two cardiac cells showing mitochondria (Mi) and stair step configurations of intercalated disks (ID) in longitudinal sections of dog papillary muscle.



Figure 3.

Longitudinal section of a normal dog papillary muscle cell reveals most of the repeating sarcomere structures. Thick and thin filaments exhibit typical banding pattern (A, I, Z, M). Large mitochondria with tightly packed cristae are found along and between the usually large myofilament bundles. Microtubules (Mt), glycogen (G) and profiles of sarcoplasmic reticulum (SR) are visible in the planes between myofibrils. T‐tubules (T) and terminal sacs of sarcoplasmic reticulum form triads. Intermediate filaments (IF) oriented transverse to the myofibril axis are visible near T‐tubules. Note portion of mitochondrion tracking along the microtubule (arrow) 98.

Reprinted by permission of Rockefeller University Press


Figure 4.

Artist's sketch of cardiac muscle showing cut‐away three‐dimensional view of several sarcomeres. A = A‐band; I = I‐band; ID = intercalated disc 98.

Reprinted by permission of Rockefeller University Press


Figure 5.

Guinea pig papillary muscle in thin longitudinal section. Microtubules (arrows), intermediate filaments and sarcoplasmic reticulum (SR) profiles are visible around the myofilament bundles and the fenestrated collar (FC) of the SR.



Figure 6.

Longitudinal section of normal dog cardiac muscle cell. Thick and thin filaments of A‐band hexagonal lattice are shown in two different orientations (A) with respect to this longitudinal plane of section through the middle of a myofibril. Mitochondrial profiles appear flattened in this view (refer to diagram in Figure 4). Note variation in Z‐width (arrows) and the change in orientation of Z‐lattice with respect to the plane of section.



Figure 7.

Interstitial area between rabbit myocytes, ultrarapidly frozen, freeze‐fractured, and then etched. The banded collagen fibrils are abundant and fill the interstitial space. With etching, the microthread network is evident as an extensive weave connecting collagen fibril to fibril 347.

Reprinted by permission of Academic Press


Figure 8.

High‐magnification micrograph of deep‐etched replica showing the collagen fibril microthread meshwork. The intertangled network that bridges and wraps around the collagen fibrils is visible in three‐dimensional array. Granules of ∼8–10 nm diameter are apparent at branch points of the microfibril‐microthread lattice (arrow) 347.

Reprinted by permission of Academic Press


Figure 9.

Freeze‐fractured, deep‐etched replica from unfixed ultrarapidly frozen rabbit heart exposed to 0‐Ca perfusion. The external lamina (el) is seen pulled back from the surface of the myocyte sarcolemma. The attachment of the external lamina is maintained at several sites by trabeculae (arrows). The demarcation between the bilayer surface of the cell and the fractured P face of the membrane is clearly visible (arrowhead) 347.

Reprinted by permission of Academic Press


Figure 10.

Freeze‐fractured, deep‐etched replica from unfixed ultrarapidly frozen rabbit heart exposed to 0‐Ca perfusion. This lower magnification micrograph should be compared to Figure 10. As in that figure, the external lamina (el) is pulled away from the sarcolemma but attached by trabeculae (arrows). Arrowhead indicates the demarcation between the bilayer cell surface and the fractured P face of the membrane 347.

Reprinted by permission of Academic Press


Figure 11.

Freeze‐etch micrograph of unfixed ultrarapidly frozen rabbit papillary muscle. At this magnification, the connecting matrix of fine fibrils in between and connecting the collagen and the muscle surface is visible (arrows). In addition to the collagen bundle fibrils, individual 54 nm diameter collagen fibrils are visible at the myocyte cell surface (myo) 75.

Reprinted by permission of S. Karger


Figure 12.

Another view of unfixed ultrarapidly frozen rabbit papillary muscle. The regularly arranged trabeculae of the external lamina of the myocyte appear to insert directly into the bilayer. The series of linkages from collagen to myocyte membrane is visible. External lamina trabeculae of ‘posts’ (arrow) insert or attach to the bilayer. A fine line marks the boundary between the outer surface and the P face of the bilayer (arrowheads) 75.

Reprinted by permission of S. Karger


Figure 13.

Freeze‐etch electron micrograph of 4 day‐old rat myocyte. This high‐magnification micrograph shows that by 4 days the cell surface and extracellular matrix fibrils are similar in density and organization to the adult. The trabeculae that link the external lamina into the bilayer are clearly visible (arrows) 75.

Reprinted by permission of S. Karger


Figure 14.

Conventionally prepared (2% tannic acid present) thin‐section electron micrograph shows the interstitial space between a rabbit myocyte (MYO) on the left and a capillary (CAP) on the right. The collagen fibrils run parallel to the long axis of the myocyte, with some collagen fibrils branching laterally to link with the myocyte cell surface and, on the other side, to the capillary. The individual structures involved in the linkages are not clearly visible in this type of preparation 75.

Reprinted by permission of S. Karger


Figure 15.

High‐magnification freeze‐etch micrograph depicting collagen fibrils from adult rat heart. Compare to neonatal material shown in Figure 16 75.

Reprinted by permission of S. Karger


Figure 16.

High‐magnification freeze‐etch micrograph depicting collagen fibrils from 4 day‐old neonatal rat heart. The collagen fibrils and the extensive connections linking them, microthreads, microfibrils, and granules, appear similar to that in the adult shown in Figure 15 75.

Reprinted by permission of S. Karger


Figure 17.

Grazing profiles of cell membrane (intercalated disk = ID, calveolae = arrows) of dog papillary muscle showing relation of extracellular components (collagen = Co) to intracellular features (mitochondria = Mi) at the cell surface.



Figure 18.

Cross section of dog papillary muscle showing cross‐cut collagen (Co) within extracellular matrix. Appearance of clear spaces is due to extraction during chemical fixation and an artifact of preparation. Note tufts of dense material just beneath the sarcolemma in cell at level of Z‐bands (arrows).



Figure 19.

Longitudinal section of dog papillary muscle showing cross‐cut profiles of T‐tubules (T) with lumen contents the same density as the extracellular matrix (collagen = Co) at the cell surface.



Figure 20.

Sarcolemma and T‐tubule (T) at cell surface is shown in longitudinal section of dog papillary muscle. Note varying shape of large mitochondrion (Mi) with microtubule (Mt) spanning the myofibril surface at an angle. T‐tubule lumen contains extracellular matrix material. The grazing cut of the large T‐tubule membrane shows the sarcoplasmic reticulum (SR) and intermediate filaments (IF) overlying a Z‐band not visible in this very thin section. Profiles of myofilaments show that the plane of section is not exactly longitudinal with respect to the lattice plane of the hexagonal arrangement of thick and thin filaments.



Figure 21.

A longitudinal section at same magnification as in Figure 20 shows fibroblast enmeshed in extracellular matrix. Indentations of the sarcolemma of this muscle cell indicate T‐tubules (T), but the section plane is not through the middle of the tubule to show the full extent of the lumen.



Figure 22.

A longitudinal section of dog papillary muscle at higher magnification than Figures 20 and 21 partly through the middle of the T‐tubule (T) shows invagination of the sarcolemma, the extracellular matrix material, the diads and triads (arrows) formed with adjacent sarcoplasmic reticulum (SR), the outpocketing of the T‐tubule membrane, a bristle‐coated vesicle emerging (arrowhead) and the subjacent SR and intermediate filaments (IF). Note the good alignment with the Z‐bands in the adjacent myofilament bundle and how the mitochondria conform to the space between adjacent T‐tubules.



Figure 23.

Cross section of guinea pig papillary muscle showing cross‐cut microtubules (arrows) distributed around the surface of the nucleus as well as between myofilament bundles.



Figure 24.

Longitudinal section of guinea pig papillary muscle showing longitudinal profiles of microtubules (arrows) near the nucleus.



Figure 25.

Cross section of rat papillary muscle showing microtubules around the nucleus (arrows). This muscle has been stretched in a relaxing solution. Note how many microtubules 27 can be seen when they are aligned perpendicular to the plane of section.



Figure 26.

Longitudinal section of contracted dog papillary muscle showing longitudinal profiles of microtubules (arrows) coming in and out of the plane of section near convoluted nucleus 98.

Reprinted by permission of Rockefeller University Press


Figure 27.

Cross section of dog papillary muscle at level of Z‐band showing cross‐sectional profiles of microtubules (arrows), longitudinal profiles of intermediate filaments (IF), sarcoplasmic reticulum (SR) adhering to myofilament bundles with specialized regions of SR forming a complex with the T‐tubule (arrowheads), and glycogen.



Figure 28.

Cross‐sectional profiles of microtubules (arrows) in rat papillary muscle at higher magnification showing their location next to mitochondria (Mi) and just outside the profiles of the Sarcoplasmic reticulum at the level of the Z‐bands and at the A–I junction.



Figure 29.

Cross section of dog papillary myofilament bundles at the level of the A‐band showing microtubule profiles (arrows) near mitochondria. The microtubules and membranes of the mitochondria are enhanced by treatment of muscle with 8% tannic acid before post‐fixation with osmium tetroxide.



Figure 30.

Longitudinal section of dog papillary muscle showing microtubules (arrows) at cell surface. Three T‐tubule profiles are evident (T). Microtubules arch across the surface of the myofilament bundles. Note also varying shapes of mitochondrial profiles. Portion of fibroblast is visible between two cells.



Figure 31.

Structure of myocardial cells at the level of light and electron microscopy is portrayed. Top: A portion of ventricular myocardium with branching muscle cells enmeshed in collagen. Nuclei are centrally placed and intercalated disks contain sites for end‐to‐end attachment of cells. Middle: Ultrastructure of portions of two cells in a cutaway view displaying the arrangement of myofibrils. A network of intermediate filaments, which surrounds the myofibrils like a cage, is periodically anchored to cell membrane plaques at the Z‐bands and at transverse regions of the intercalated disks. Bottom: Within the sarcomeres, the contractile units of the muscle delimited at each end by a Z‐band consist of three sets of filaments. Thick filaments containing primarily myosin are located in the A‐band; thin filaments containing actin, tropomyosin, and troponin, and thin elastic filaments of titin extend from each Z‐band toward the middle of the sarcomere. The thick and thin filaments interdigitate regularly to form a hexagonal array seen in cross section. The titin filaments attach periodically along the thick filament. The Z‐band is a lattice of axial and cross‐connecting Z‐filaments. In the Z‐band, the ends of the thin filaments from adjacent sarcomeres overlap and interdigitate in a centered tetragonal array and are held together periodically by cross‐connecting Z‐filaments 104.

Reprinted by permission of the American Physiological Society


Figure 32.

Cross section of cat papillary muscle showing longitudinal profile of intermediate filaments (IF) near Z‐bands and intercalated disk (ID). Long profile of T‐tubule with portions of two diads (one at each end, arrows) near the intercalated disk (see diagram in Figure 4 for orientation). Note gap junction at lower right (arrowhead).



Figure 33.

Longitudinal section of dog papillary muscle showing intermediate filament bundles (IF) near cell surface at desmosome‐like regions extending across the surface of the myofilaments at the Z band level and intermediate filament bundles at three other Z‐bands.



Figure 34.

Longitudinal section of dog papillary muscle showing intermediate filament bundles (IF) at three different Z‐band levels spanning several myofilament bundles. Note profiles of sarcoplasmic reticulum (SR) and microtubules (arrows).



Figure 35.

Longitudinal section of dog papillary muscle showing intermediate filaments and microtubules.



Figure 36.

Cross section of rat papillary muscle showing mitochondria and myofilament bundles, the two most prominent features of the cardiac sarcomere, together with two cytoskeletal components—cross‐cut profiles of microtubules (Mt) and longitudinal profiles of intermediate filaments (IF). Note caveolae of sarcolemma of adjacent cell (arrows).



Figure 37.

Cross section of rat papillary muscle in interior of cell showing hexagonal arrangement of thick and thin contractile filaments in M‐band and A‐band. A T‐tubule profile (T) at the level of the Z‐band shows the region of contact with the sarcoplasmic reticulum specialized for excitation–contraction coupling and the “feet” structures (arrowheads).



Figure 38.

Longitudinal section of dog papillary muscle showing long mitochondrial profile (Mi) spanning three sarcomeres. Note bowing profile of microtubule (arrow) aligning with surfaces of three different mitochondrial profiles and the partially extracted lipid droplet (Li) between two mitochondrial profiles.



Figure 39.

Longitudinal section of dog papillary muscle showing relationship between varying shapes of mitochondrial profiles (Mi) and the intermediate filament (IF) bundles that maintain registration between adjacent Z‐bands perpendicular to the myofibril axis. Note that the myofilament bundles are not aligned exactly in the longitudinal plane of section.



Figure 40.

Longitudinal section of dog papillary muscle showing the relationship between longitudinal profiles of microtubules (arrows), sarcoplasmic reticulum, T‐tubules (T), intermediate filaments (IF) and adjacent myofilament bundles 98.

Reprinted by permission of Rockefeller University Press


Figure 41.

Cross section of myofilament bundles from papillary muscle showing A, I and Z‐bands. Compare with Figure 6 to see corresponding appearance in a longitudinal section of papillary muscle.



Figure 42.

Cross section of rat papillary myofilament bundle at level of Z‐band showing one of the unusual myofibril shapes.



Figure 43.

Thin longitudinal section of dog papillary myofibril. Periodicities along thick and thin filaments can be seen by viewing figure from above at 45 degrees. Striations within M‐band and Z‐lattices can be seen at this magnification. Note N‐lines (arrowheads).



Figure 44.

Thick and thin filaments in hexagonal array in cross section of A‐band can be seen by viewing the figure from above at 45 degrees. Try rotating the figure as you view to get best perspective.



Figure 45.

Cross section of dog papillary myofibril at level of M‐band and edge of A‐band. Note distinct triangular appearance of cross‐cut thick filaments and the filaments connecting all six thick filaments and a central thick filament in several arrays in middle of M‐band. Some thin filaments penetrate into the H‐zone because some are much longer than others.



Figure 46.

Cross section of sarcomere near nucleus exhibits M‐band ordering of thick filaments. Adjacent myofilament bundles are at I‐band level. Not all myofibrils are in exact register across the cell in cardiac muscle.



Figure 47.

Thin filaments in I‐band lack precise symmetry, are not random, but exhibit nearest‐neighbor ordering. Note connections between some pairs of thin filaments in this cross section of dog papillary muscle.



Figure 48.

Cross section of Z‐band lattice of a single sarcomere. The basket weave, or bw, lattice appearance predominates in this unstimulated cardiac muscle.



Figure 49.

Cross section of unstimulated dog papillary muscle showing portion of Z‐band exhibiting two different lattice appearances: the basket weave pattern (bw) predominates, but a small region of small square pattern (ss) is visible at far right.



Figure 50.

Longitudinal section of Z‐band anchored near the sarcolemma. The chevron pattern typical of this 24 nm (1,0) orientation of the Z‐lattice is shown. Thin filaments of adjacent sarcomeres interdigitate and the distance between adjacent thin filaments from the same sarcomere is 24 nm.



Figure 51.

Longitudinal section of Z‐band showing intermediate filaments (IF) going between adjacent Z‐bands and around periphery of Z‐lattice.



Figure 52.

Longitudinal section of Z‐band lattice exhibiting chevron appearance typical of the 24 nm (1,0) orientation. This Z lattice is especially uniform with respect to the plane of section, yet there are 3–4 subunits visible at the left, whereas at the bottom only two are visible. This is seen most easily if viewed at an angle of 45 degrees.



Figure 53.

Longitudinal section of Z‐band in same orientation as Figure 52, but the sarcomere is longer. The appearance of the Z‐lattice is the same. Experimental evidence shows that passive stretch does not induce a change in lattice appearance or spacing. Intermediate filaments (IF) are visible between adjacent Z‐bands.



Figure 54.

Longitudinal section of Z‐band in 17 nm 1 orientation (17 is half‐diagonal of a 24 nm square). Thin filaments appear to go straight through the Z‐band, when in fact the overlapping ends of the thin filaments form a centered square arrangement.



Figure 55.

Longitudinal section from human atrial biopsy showing widening of several Z‐bands. Note loss of exact registration of thick and thin filaments within the sarcomeres. Edges of I, A, and M‐bands are uneven.



Figure 56.

Longitudinal section of normal dog cardiac sarcomeres showing Z‐bands of different widths. The Z‐band at the bottom left has the usual appearance, is well centered in the I‐band, and the M‐bands of adjacent sarcomeres are in register. The widened Z‐band in the next sarcomere of the same myofilament bundle is taking up more of the I‐band. The two widest Z‐bands flanking a barrel‐shaped A‐band take up most of the I‐band.



Figure 57.

Longitudinal section of papillary muscle taken from another normal dog showing the profile of Z‐band material spanning the entire sarcomere length and maintaining continuity with adjacent sarcomeres both in the same myofilament bundle and in the adjacent myofilament bundle.



Figure 58.

Z‐crystals in aged cat myocardium in several different orientations with respect to plane of section. All are aligned along the myofibril axis and all have thin filaments emerging into normal‐looking A‐bands with normal Z‐bands at the opposite ends of these sarcomeres.



Figure 59.

Longitudinal section of Z‐crystal or rod in normal dog papillary muscle. Note continuity of axial filaments with thin filaments in the adjacent I‐band and chevron pattern of normal Z‐band. The three‐dimensional reconstructions of Z‐rod and normal Z‐band are very similar.



Figure 60.

Typical sarcomere seen in normal myofibers adjacent to dog heart cell containing Z‐crystal shown in Figure 59. The A‐band length is 1.56 μm. The 17 nm 1 orientation of the Z‐band (arrowhead) where the thin filaments appear to pass through the Z‐band lattice is one of the two orientations of the tetragonal Z‐lattice that gives maximal reinforcement to the axial filaments.



Figure 61.

High‐voltage electron micrograph of half‐micron section of dog cardiac muscle. The exact alignment of thick and thin filaments within each sarcomere gives reinforcement of the banding patterns, Z, I, A, M, but registration of adjacent myofilament bundles is not exact. Compare to high‐magnification cross sections of thin sections of myofilaments shown in Figures 37,41, and 46. Note the abundance of glycogen granules (G) in these thick sections.



Figure 62.

High‐voltage electron micrograph of half‐micron section of cardiac muscle. Note the variation in Z‐band width (i.e. number of lattice subunits in axial direction) occurring within a region of the same lattice orientation (arrows) and occurring in a region of changing orientation toward the top of the figure. The periodicities within the I, A, and M‐bands are clearly visible. The glycogen granules (G) appear as black dots, mostly in I‐band but also one or two in M‐band.



Figure 63.

Electron micrograph of unstimulated cardiac muscle in cross section showing the Z‐band in the bw form and the adjacent A‐bands.



Figure 64.

Electron micrograph of a cross section of soleus perfusion‐fixed during a tetanic contraction in situ. The bw form of the Z‐lattice is predominant 103.

Reprinted by permission of Kluwer Academic and Lippencott‐Raven Publishers


Figure 65.

Electron micrograph of a cross section of rat soleus muscle stretched in a muscle myograph in 100 mM PIPES buffer by applying a load of 3 g, adjusting for stress relaxation and fixing at the final length achieved after 30 min at 3 g load. The Z‐lattice exhibits the small square (ss) pattern.



Figure 66.

Cross section of rat soleus muscle stretched in a muscle myograph in 100 mM PIPES buffer by applying a load of 6 g, adjusting for stress relaxation, and fixing at the final length achieved after 30 min at 6 g load. The average sarcomere length of this muscle preparation was 2.5 μm. The Z‐band exhibits the small square (ss) lattice pattern.



Figure 67.

Longitudinal section of adult rat soleus muscle stretched by a 6 g load in a bath containing 5 mM EGTA in 100 mM PIPES buffer, pH 7.2. At least five distinct stripes (arrowheads) are present in the I‐band on either side of the Z‐band, four of which are within a region of increased electron density as well as the N2 line (arrow). Sarcomere lengths in this section average 3.35. Section is 200 nm thick, stained with uranyl acetate and Sato's lead stain, and photographed at 200 kV.



Figure 68.

Cross section of rat papillary muscle stretched in a bath containing 5 mM EGTA in 100 mM PIPES buffer, pH 7.2. Note the uniform small square (ss) appearance of the cardiac Z‐band in relaxed muscle. Empty T‐tubules and dark granules in mitochondria are both signs of altered calcium distribution in the cell due to chelation of calcium by EGTA.



Figure 69.

Electron micrograph of EGTA treated cardiac muscle in cross section showing the Z‐band in the ss form 102.

Reprinted by permission of the American Physiological Society


Figure 70.

A projection of a 25 nm‐thick longitudinal section taken from a three‐dimensional reconstruction of the Z‐band from unstimulated skeletal muscle. Axial filaments enter the Z‐band from top and bottom of the figure (arrowheads). Crossconnecting Z‐filaments appear to connect the axial filaments in this “chevron” (1,0) orientation projection (scale bar = 10nm) 276.

Reprinted by permission of Rockefeller University Press


Figure 71.

A stereo‐shaded solid rendering of the three‐dimensional reconstruction of Plate 1. Compare to Figures 72 and 74; scale bar = 10 nm.



Figure 72.

Stereo‐shaded solid rendering of a longitudinal section from a three‐dimensional reconstruction of rigor skeletal muscle. Axial filaments enter from the top and bottom of the figure and are interconnected at the edges of the Z‐band by an array of cross‐connecting Z‐filaments. There appear to be fewer crossconnections in this rigor Z‐band than in the unstimulated muscle shown in Plate 1 and Figures 70 and 71. The vertical spacing between crossconnections is larger than in the unstimulated muscle; scale bar = 10 nm.



Figure 73.

Projection of a 20 nm longitudinal slice from a preliminary three‐dimensional reconstruction of unstimulated cardiac Z‐band. Compare similar projection view of longitudinal slice from three‐dimensional reconstruction of unstimulated skeletal muscle sseen in Figure 70; scale bar = 10 nm.



Figure 74.

Grey‐scale shaded solid stereo pair of a portion of a three‐dimensional reconstruction of the Z‐band lattice in unstimulated rat cardiac muscle, shown in a longitudinal orientation. This muscle exhibits the basket weave form of the lattice in cross section. Thin axial filaments enter the Z‐band from the top and bottom the figure, where they are interconnected by an array of Z‐band cross‐connecting filaments. In this view, the cross‐connecting filaments attach at intervals of ∼20 nm along the axial filament; scale bar = 10 nm.

References
 1. Amrein, M. and H. Gross. Scanning tunneling microscopy of biological macromolecular structures coated with a conductive film. Scanning Microsc. 6: 335–342, 1992.
 2. Ashurst, D. E. The Z‐line: its structure and evidence for the presence of connecting filaments. In Tregear, R. T., ed., Insect Flight Muscle Amsterdam: North‐Holland 1977: 57–73.
 3. Ayoob, J. C., Turnacioglu, K. K., Mittal, B., J. M. Sanger, and J. W. Sanger. Targeting of cardiac muscle titin fragments to the Z‐bands and dense bodies of living muscle and non‐muscle cells. Cell Motil. Cytoskel. 45: 67–82, 2000.
 4. Bard, F. and C. Franzini‐Armstrong. Extra actin filaments at the periphery of skeletal muscle myofibrils. Tissue Cell 23: 191–197, 1991.
 5. Barer, R. The structure of the striated muscle fibre, Biol. Rev. 23: 159–200, 1948.
 6. Barnard, T. Rapid freezing techniques and cryoprotection of biomedical specimens. Scanning Microsc. 1: 1217–1224, 1987.
 7. Baskin, T. I., D. D. Miller, J. W. Vos, J. E. Wilson and P. K. Hepler. Cryofixing single cells and multicellular specimens enhances structure and immunocytochemistry for light microscopy. J. Microsc. 182 (Pt 2): 149–161, 1996.
 8. Becker, R. P. and J. S. Geoffroy. Backscattered electron imaging for the life sciences: Introduction and index to applications—1961 to 1980. Scanning Electron Microsc. 4: 195–206, 1981.
 9. Beesley, J. F. Bioapplication of colloidal gold in microbiological immunocytochemistry. Scanning Microsc. 2: 1055–1068, 1988.
 10. Behr, T., P. Fischer, W. Muller‐Felber, M. Schmidt‐Achert and D. Pongratz. Myofibrillogenesis in primary tissue cultures of adult human skeletal muscle: expression of desmin, titin, and nebulin. Clin. Invest. 72: 150–5, 1994.
 11. Belkin, A. M., N. I. Zhidkova and V. E. Koteliansky. Localization of talin in skeletal and cardiac muscles. FEBS Lett 200: 32–36, 1986.
 12. Bennett, P. M. Decrease in section thickness on exposure to the electron beam; the use of tilted sections in estimating the amount of shrinkage. J. Cell Sci. 15: 693–701, 1974.
 13. Berne, R. and M. Levy. Contraction of muscle cells. In Physiology 2nd ed. St. Louis: C. V. Mosby, 1988: 315–334.
 14. BishopS. F. and C. R. Cole. Ultrastructure changes in canine myocardium with right ventricular hypertrophy and congestive heart failure. Lab. Invest. 20: 219–229, 1969.
 15. Blanchard, A., O. Vasken and D. Critchley. The structure and function of alpha‐actinin. J. Musc. Res. Cell Motil. 10: 280–289, 1989.
 16. Borg, T. K., and J. B. Caulfield. Morphology of connective tissue in skeletal muscle. Tissue Cell 12: 197–207, 1980.
 17. Bowman, W. On the minute structure and movements of voluntary muscle. Phil. Trans. R. Soc. Lond. 130: 457–501, 1840. Bowman coined the term “sarcolemma,” and pointed out that skeletal muscle contraction is accompanied by a decrease in the distance between the transverse striations of the muscle fibril.
 18. Boyde, A. Confocal optical microscopy. In Duke, P. J. and A. J. Michette, eds. Modern Microscopies—Techniques and Applications, New York: Plenum, 1990: 185–204.
 19. Bozzola, J. J. and L. D. Russell. In Jones, and Bartlett Electron Microscopy—Principles and Techniques for Biologists. Boston: 1992: 108–120; 204; 44; 27–31; 110; 306–328.
 20. Braunfeld, M. B., A. J. Koster, J. W. Sedat, and D. A. Agard. Cryo Automated electron tomography: towards high‐resolution reconstructions of plastic‐embedded structures, J. Microsc. 174: 75–84, 1994.
 21. Briarty, L. G. Stereology: methods for quantitative light and electron microscopy. Sci. Prog. 62: 1–32, 1975.
 22. Bullough, P. and R. Henderson. Use of spot‐scan procedure for recording low‐dose micrographs of beam‐sensitive specimens, Ultramicroscopy 21: 223–230, 1987.
 23. Burns, A. R., S. I. Simon, G. L. Kukielka, J. L. Rowen, H. Lu, L. H. Mendoza, E. S. Brown, M. L. Entman and C. W. Smith. Chemotactic factors stimulate CD18‐dependent canine neutrophil adherence and motility on lung fibroblasts. J. Immunol. 156: 3389–3401, 1996.
 24. Burridge, K. and P. Mangeat. An interaction between vinculin and talin. Nature 308: 744–46, 1984.
 25. Burridge, K. and L. Connell. A new protein of adhesion plaques and membrane ruffles. J. Cell Biol. 97: 359–367, 1983.
 26. Burridge, K. and L. Connell. Talin: a cytoskeletal component concentrated in adhesion plaques and other sites of actin–membrane interaction. Cell Motil. 3: 405–417, 1983.
 27. Caldwell, J. E., S. G. Heiss, V. Mermall and J. A. Cooper. Effects of CapZ, an actin capping protein of muscle, on the polymerization of actin. Biochemistry 28: 8506–8514, 1989.
 28. Campbell, S. E., A. M. Gerdes and T. D. Smith. Comparison of regional differences in cardiac myocyte dimensions in rats, hamsters, and guinea pigs. Anat. Rec. 219: 53–59, 1987.
 29. Carlsson, E., B. K. Grove, T. Wallimann, H. M. Eppenberger and L. E. Thornell. Myofibrillar M‐based proteins in rat skeletal muscles during development. Histochemistry 95: 27–35, 1990.
 30. Cartwright, J., Jr. and M. A. Goldstein. Microtubules in the heart muscle of the postnatal and adult rat. J. Mol. Cell Cardiol. 17: 1–7, 1985.
 31. Casella, J. F., J. Maack and S. Lin. Purification and initial characterization of a protein from skeletal muscle that caps the barbed ends of actin filaments. J. Biol. Chem. 261: 10915–21, 1986.
 32. Casella, J. F., S. W. Craig, D. L. Maack and A. E. Brown. CapZ(36/32), a barbed end actin‐capping protein, is a component of the Z‐line of skeletal muscle. J. Cell Biol. 105: 371–379, 1987.
 33. Caulfield, J. B. and T. K. Borg. The collagen network of the heart. Lab. Invest. 40: 364–372, 1979.
 34. Chen, F. B. Mottino, T. S. Klitzner, K. D. Philipson and J. S. Frank. Distribution of the Na+/Ca2+ exchange protein in developing rabbit myocytes. Am. J. Physiol. 268 (Cell Physiol. 36): C1126–C1132, 1995.
 35. Cheng, N. and J. F. Deatherage. Three‐dimensional reconstruction of the Z disk of sectioned bee flight muscle. J. Cell Biol. 108: 1761–1774, 1989.
 36. Chowrashi, P. K. and F. A. Pepe. The Z‐band: 85000‐dalton amorphin and alpha‐actinin and their relation to structure. J. Cell Biol. 94: 565–573, 1982.
 37. Colliex, C., and C. Mory. Scanning transmission electron microscopy of biological structures, Biol. Cell 80: 175–180, 1994.
 38. Cosslett, V. E. Radiation damage in the high resolution electron microscopy of biological materials: a review. J. Microsc. 113: 113–129, 1978.
 39. Cox, G. Trends in confocal microscopy. Micron 24: 237–247, 1993.
 40. Craig, R., L. Alamo and R. Padron. Structure of the myosin filaments of relaxed and rigor vertebrate striated muscle studied by rapid freezing electron microscopy. J. Mol. Biol. 228: 474–487, 1992.
 41. Craig, S. W. and J. V. Pardo. Gamma actin, spectrin, and intermediate filament proteins colocalize with vinculin at costameres, myofibril‐to‐sarcolemma attachment sites. Cell Motil. 3: 449–462, 1983.
 42. Crowther, R. A., D. J. DeRosier and A. Klug. Three‐dimensional reconstruction from projections and its application to electron microscopy. Proc. R. Soc. Lond. A 317: 319–340, 1970.
 43. Crowther, R. A. and P. K. Luther. Three‐dimensional reconstruction from a single oblique section of fish muscle M‐band. Nature 307: 569–570, 1984.
 44. Crowther, R. A., P. K. Luther and K. A. Taylor. Computation of a three dimensional image of a periodic specimen from a single view of an oblique section. Electron Microsc. Rev. 3: 29–42, 1990.
 45. Dalen, H., P. Scheie, R. Nassar, T. High, B. Scherer, I. Taylor, N. R. Wallace and J. R. Sommer. Cryopreservation evaluated with mitochondrial and Z line ultrastructure in striated muscle. J. Microsc. 165 (Pt 2): 239–254, 1992.
 46. Danilatos, G. D. Introduction to the ESEM instrument, Microsc. Res. Tech. 25: 354–361, 1993. This issue of Microscopy Research and Technique also contains several excellent articles detailing ESEM studies on different systems.
 47. Davey, D. F. The relation between Z‐disk lattice spacing and sarcomere length in sartorius muscle fibers from Hyla cerula. Aust. J. Biol. Med. Sci. 54: 441–447, 1976.
 48. Deatherage, J. F., N. Cheng and B. Bullard. Arrangement of filaments and cross‐links in the bee flight muscle Z disk by image analysis of oblique sections. J. Cell Biol. 108: 1775–1782, 1989.
 49. DeRosier, D. J. The reconstruction of three‐dimensional images from electron micrographs. Contemp. Physics 12: 437–452, 1971.
 50. Dierksen, K., D. Typke, R. Hegerl, A. J. Koster and W. Baumeister. Towards automatic electron tomography. Ultramicroscopy 40: 71–87, 1992.
 51. Dolber, P. C. and M. S. Spach. Conventional and confocal fluorescence microscopy of collagen fibers in the heart. J. Histochem. Cytochem. 41: 465–469, 1993.
 52. Dykstra, M. J. Biological Electron Microscopy—Theory, Techniques, and Troubleshooting, New York: Plenum, 1992: 131–133; 237; 8–9; 17–18; 171–181; 251–258; 247; 264–267; 270; 249; 295–296; 297–308; 315–318.
 53. Eberth, C. J. Die Elemente der quergestreiften Muskeln, Arch. Pathol. Anat. Physiol. 1866, as quoted by von Palczewska (1910) and by Jordan (1911).
 54. Edwards, R. J., Goldstein, M. A., Schroeter, J. P. and Sass, R. L. The Z band lattice in skeletal muscle in rigor. J. Ultrastruct. Mol. Struct. Res. 102: 59–65, 1989.
 55. Eisenberg, B. R. and R. L. Milton. Muscle fiber termination at the tendon in the frog's sartorius: a stereological study. Am. J. Anat. 171: 273–284, 1984.
 56. Eisenberg, B. R. and Salmons, S. The reorganization of subcellular structure in muscle undergoing fast‐to‐slow type transformation. A stereological study. Cell Tissue Res. 220: 449–471, 1981.
 57. Elliott, G. F., J. Lowy and B. M. Millman. Low‐angle X‐ray diffraction studies of living striated muscle during contraction. J. Mol. Biol. 25: 31–45, 1967.
 58. Engel, A. and C. Colliex. Application of scanning transmission electron microscopy to the study of biological structure. Current Opinion Biotech. 4: 403–411, 1993.
 59. Egerton, R. F. Electron Energy‐Loss Spectroscopy in the Electron Microscope. New York: Plenum, 1989.
 60. Erickson, H. P. and A. Klug. Measurement and compensation of defocussing and aberrations by Fourier processing of electron micrographs, Phil. Trans. R. Soc. Lond. 261: 105–118, 1971.
 61. Ervasti, J. M. and K. P. Campbell. A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J. Cell Biol. 122: 809–823, 1993.
 62. Everhart, T. E. and T. L. Hayes. The scanning electron microscope. Sci. Am. 226: 54–68, 1972.
 63. Fardeau, M. Ultrastructure de fibres musculaires squelettiqes (1). Presse Med. 77: 1341–1344, 1969.
 64. Faulkner, G., A. Pallavincini, E. Formentin, A. Comelli, C. Ievolella, S. Trevisan, G. Bortello, P. Scannapieco, M. Salamon, V. Mouly, G. Valle, and G. Lanfranchi. ZASP: a new Z‐band alternatively spliced PDZ‐motif protein. J. Cell Biol. 146: 465–475, 1999.
 65. Fawcett, D. W. and N. S. McNutt. The ultrastructure of the cat myocardium I. Ventricular papillary muscle. J. Cell Biol. 42: 1–45, 1969.
 66. Ferrans, V. J. and W. C. Roberts. Inter‐myofibrillar and nuclear‐myofibrillar connections in human and canine myocardium. An ultrastructural study. J. Mol. Cell. Cardiol. 5: 247–257, 1973.
 67. Firtel, M. and T. J. Bereridge. Scanning probe microscopy in microbiology. Micron 26: 347–362, 1995.
 68. Flegler, S. L., J. W. Heckman and K. L. Klomparens. Scanning and Transmission Electron Microscopy, An Introduction, New York: W. H. Freeman, 1993: 173–196; 109; 108–113.
 69. Flicker, P. F., R. A. Milligan and D. Applegate. Cryo‐electron microscopy of S1‐decorated actin filaments. Adv. Biophys. 27: 185–196, 1991.
 70. Flucher, B. E. and Franzini‐Armstrong, C. Formation of junctions involved in excitation–contraction coupling in skeletal and cardiac muscle. Proc. Natl. Acad. Sci. U.S.A. 93: 8101–8106, 1996.
 71. Forbes, M. S. and N. Sperelakis. Ultrastructure of mammalian cardiac muscle. In Sperelakis, N., ed. Physiology and Pathophysiology of the Heart. Boston: Martinus Nijhoff, 1984: 3–42.
 72. Fowler, V. M. Regulation of actin filament length in erythrocytes and striated muscle. Curr. Opin. Cell Biol. 8: 86–96, 1996.
 73. Frank, J. S., and G. A. Langer. The myocardial interstitium: Its structure and its role in ionic exchange. J. Cell Biol. 60: 586–601, 1974.
 74. Frank, J. S. and S. Beydler. Intercellular connections in rabbit heart as revealed by quick‐frozen, deep‐etched, and rotary‐replicated papillary muscle. J. Ultrastruct. Res. 90: 183–193, 1985.
 75. Frank, J. S. and R. Yung. The myocyte–connective tissue interface. In Robinson, T. F. and R. K. H. Kinne, eds. Cardiac Myocyte–Connective Tissue Interactions in Health and Disease (Issues Biomed. vol. 13). New York: Karger, 1990: 79–98.
 76. Frank, J. S., G. Mottino, D. Redi, R. S. Molday and K. D. Phillipson. Distribution of the Na+–Ca2+ exchange protein in mammalian cardiac myocytes: an immunofluorescence and immunocolloidal gold‐labeling study. J. Cell Biol. 117: 337–345, 1992.
 77. Frank, J. S., G. Mottino, F. Chen, V. Peri, P. Holland and B. S. Tuana. Subcellular distribution of dystrophin in isolated adult and neonatal cardiac myocytes. Am. J. Physiol. 267 (Cell Physiol. 36): C1707–1716, 1994.
 78. Frank, J. The role of correlation techniques in computer image processing. In Hawkes, P. W., ed. Computer Processing of Electron Microscope Images. Berlin: Springer Verlag, 1980: 187–222.
 79. Frank, J., B. F. McEwen, M. Radermacher, J. N. Turner and C. L. Rieder. Three‐dimensional tomographic reconstruction in high voltage electron microscopy. JEM Tech. 6: 193–205, 1987.
 80. Frank, J. Introduction: Principles of electron tomography. In Frank, J. ed. Electron Tomography—three‐dimensional imaging with the transmission electron microscope. New York: Plenum, 1992: 1–16.
 81. Franzini‐Armstrong, C. and D. A. Fischman. Morphogenesis of skeletal muscle fibers. In Engel, A. G. and Franzini‐Armstrong, C. eds, Myology. New York: McGraw‐Hill, 1994: 74–96.
 82. Franzini‐Armstrong, C. and A. O. Jorgensen. Structure and development of E‐C coupling units in skeletal muscle. Annu. Rev. Physiol. 56: 509–534, 1994.
 83. Fujikawa, S. Freeze‐fracture techniques. In Harris, J. R. ed., Electron Microscopy in Biology: A Practical Approach. Oxford: Oxford University Press, 1991: 173–202.
 84. Funatsu, T., H. Higuchi and S. Ishiwata. Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin. J. Cell Biol. 110: 53–62, 1990.
 85. Funatsu, T., E. Kono, H. Higuchi, S. Kimur, S. Ishiwata, T. Yoshioka, K. Maruyama and S. Tsukita. Elastic filaments in situ in cardiac muscle: deep‐etch replica analysis in combination with selective removal of actin and myosin filaments. J. Cell Biol. 120: 711–24, 1993.
 86. Furst, D. O., R. Nave, M. Osborn and K. Weber. Repetitive titin epitopes with a 42 nm spacing coincide in relative position with known A band striations also identified by major myosin‐associated proteins. An immunoelectron‐microscopical study on myofibrils. J. Cell Sci. 94: 119–125, 1989.
 87. Gabriel, B. L. Biological Scanning Electron Microscopy. New York: Van Nostrand Reinhold, 1982: 43–50.
 88. Gautel, M., E. Lehtonen and F. Pietruschka. Assembly of the cardiac I‐band region of titin/connectin: expression of the cardiac‐specific regions and their structural relation to the elastic segments. J. Musc. Res. Cell Motil. 17: 449–61, 1996.
 89. Geisler, J. G., R. J. Palmer, L. J. Stubbs, and M. L. Mucenski. Nspl1, a new Z‐band–associated protein. J. Musc. Res. Cell Motil. 20: 661–668, 1999.
 90. Gerdes, A. M. and F. H. Kasten. Morphometric study of endomyocardium and epimyocardium of the left ventricle in adult dogs. Am. J. Anat. 159: 389–394, 1980.
 91. Gerdes, A. M., J. Kriseman and S. P. Bishop. Morphometric study of cardiac muscle: the problem of tissue shrinkage. Lab. Invest. 46: 271–274, 1982.
 92. Glaeser, R. M., and K. A. Taylor. Radiation damage relative to transmission electron microscopy of biological specimens and low temperature: a review, J. Microsc. 112: 127–138, 1978.
 93. Goldmann, W. H., V. Niggli, S. Kaufmann, and G. Isenberg. Probing actin and liposome interaction of talin and talin‐vinculin complexes: A kinetic, thermodynamic, and lipid labeling study. Biochemistry 31: 7665–7671, 1992.
 94. Goldstein, J. I., D. E. Newbury, P. Echlin, D. C. Joy, A. D. Rornig Jr., C. E. Lyman, C. Fiori and E. Lifshin. Scanning Electron Microscopy and X‐Ray Microanalysis, 2nd ed. New York: Plenum, 1992: 219–230; 142; 255–259.
 95. Goldstein, M. A., J. P. Schroeter and R. L. Sass. Optical diffraction of the Z lattice in canine cardiac muscle. J. Cell. Biol. 75: 818–836, 1977.
 96. Goldstein, M. A. Ultrastructure of the ischemic myocardium. Cardiovasc. Res. Center Bull. 18: 1–33, 1979.
 97. Goldstein, M. A., J. P. Schroeter and R. L. Sass. The Z lattice in canine cardiac muscle. J. Cell Biol. 83: 187–204, 1979.
 98. Goldstein, M. A. and M. L. Entman. Microtubules in mammalian heart muscle. J. Cell. Biol. 80: 183–195, 1979.
 99. Goldstein, M. A., M. H. Stromer, J. P. Schroeter and R. L. Sass. Optical reconstruction of nemaline rods. Exp. Neurol. 70: 83–97, 1980.
 100. Goldstein, M. A., D. L. Murphy, W. B. Van Winkle and M. L. Entman. Cytochemical studies of a glycogen‐sarcoplasmic reticulum complex. J. Musc. Res. Cell Motil. 6: 177–187, 1985.
 101. Goldstein, M. A. Cardiac sarcomere. In Gotto, A. M. and R. Paoletti, eds. Arteriosclerosis Reviews, 14. New York: Raven, 1986: 183–212.
 102. Goldstein, M. A., L. H. Michael, J. P. Schroeter and R. L. Sass. Two structural states of Z bands in cardiac muscle. Am. J. Physiol. 256 (Heart Physiol. 25): H552–H559, 1989.
 103. Goldstein, M. A., J. P. Schroeter and R. L. Sass. Two structural states of the vertebrate Z band. Electron Microsc. Rev. 3: 227–248, 1990.
 104. Goldstein, M. A., J. P. Schroeter and L. H. Michael. Role of the Z band in the mechanical properties of the heart. FASEB J. 5: 2167–2174, 1991.
 105. Goldstein, M. A., R. J. Edwards and J. P. Schroeter. Cardiac morphology after conditions of microgravity during COSMOS 2044. J. Appl. Physiol. 73 (Suppl.): 94S–100S, 1992.
 106. Goldstein, M. A., J. Cheng and J. P. Schroeter. The effects of increased gravity and microgravity on cardiac morphology. Aviat. Space Environ. Med. 69: (Suppl.): A12–16, 1998.
 107. Goll, D. E., W. R. Dayton, I. Singh and R. M. Robson. Studies of the alpha‐actinin/actin interaction in the Z‐disk by using calpain. J. Biol. Chem. 266: 8501–8510, 1991.
 108. Goodman, S. L., G. M. Hodges, and D. C. Livingston. A review of the colloidal gold marker system. Scan. Elec. Microsc. (Pt 2): 133–146, 1980.
 109. Granzier, H. L. and T. C. Irving. Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments. Biophys. J. 68: 1027–1044, 1995.
 110. Gregorio, C. C., K. Trombitas, T. Centner, B. Kolmerer, G. Stier, K. Kunke, K. Suzuki, F. Obermayr, B. Herrmann, H. Granzier, H. Sorimachi, and S. Labeit. The NH2 terminus of titin spans the Z‐disc: its interaction with a novel 19‐kD ligand (T‐cap) is required for sarcomeric integrity. J. Cell Biol. 143: 1013–1027, 1998.
 111. Gruver, C. L., F. DeMayo, M. A. Goldstein and A. R. Means. Targeted developmental overexpression of calmodulin induces proliferative and hypertrophic growth of cardiomyocytes in transgenic mice. Endocrinology 133: 376–388, 1993.
 112. Guerrero, J. R. and R. Padron. The substructure of the backbone of the thick filament from tarantula muscle. Acta Microsc. 1: 63–83, 1992.
 113. Haggis, G. H. Sample preparation for electron microscopy of internal cell structure. Microsc. Res. Tech. 22: 151–159, 1992.
 114. Hainfeld, J. F. Site‐specific cluster labels. Ultramicroscopy 46: 135–144, 1992.
 115. Hainfeld, J. F. and F. R. Furuya. A 1.4 nm gold cluster covalently attached to antibodies improves immunolabeling. J. Histochem. Cytochem. 40: 177–184, 1992.
 116. Hall, T. A. Suggestions for the quantitative X‐ray microanalysis of thin sections of frozen‐dried and embedded biological tissues. J. Microsc. 164: 67–79, 1991.
 117. Hansma, P. K., V. B. Elings, O. Marti and C. E. Bracker. Scanning tunneling microscopy and atomic force microscopy: application to biology and technology. Science 242: 209–216, 1988.
 118. Harford, J., P. Luther and J. Squire. Equatorial A‐band and I‐band X‐ray diffraction from relaxed and active fish muscle—further details of myosin crossbridge behavior. J. Mol. Biol. 239: 500–512, 1994.
 119. Harris, P. and P. A. Poole‐Wilson, eds. Advances in Myocardiology, vol. 5, New York: Plenum, 1985.
 120. Haselgrove, J. C. X‐ray evidence for conformational changes in the myosin filaments of vertebrate striated muscle. J. Mol. Biol. 92: 113–143, 1975.
 121. Hasselink, M. K., H. Kuipers, P. Geurten, H. Van Straaten. Structural muscle damage and muscle strength after incremental numbers of isometric and forced lengthening contractions. J. Musc. Res. Cell Motil. 17: 335–341, 1996.
 122. Hausmanowa‐Petrusewicz, I., A. Fidzianska and B. Badurska. Unusual course of nemaline myopathy. Neuromusulc. Disord. 2: 413–418, 1992.
 123. Hawkes, P. W. The electron microscope as a structure projector. In J. Frank, ed., Electron Tomography—Three‐Dimensional Imaging with the Transmission Electron Microscopy. New York: Plenum, 1992: 17–38.
 124. Hayat, M. A. Introduction to Scanning Electron Microscopy. Baltimore: University Park Press, 1978, 96 p.
 125. Hermann, R., P. Walther and M. Muller. Immunogold labeling in scanning electron microscopy. Histochem. Cell Biol. 106: 31–39, 1996.
 126. Herrara, G. A. Ultrastructural immunolabeling: a general overview of techniques and applications. Ultrastruct. Pathol. 16: 37–45, 1992.
 127. Hesketh, J. Translation and the cytoskeleton: a mechanism for targeted protein synthesis. Mol. Biol. Rep. 19: 233–243, 1994.
 128. Hippe‐Sanwald, S. Impact of freeze substitution on biological electron microscopy. Microsc. Res. Tech. 24: 400–422, 1993.
 129. Hirakow, R. and T. Gotoh. A quantitative ultrastructural study on developing rat heart. In M. Lieberman, and T. Sano, eds., Developmental and Physiological Correlates of Cardiac Muscle. New York: Raven, 1975: 37–49.
 130. Hirose, K. C. Franzini‐Armstrong, Y. E. Goldman and J. M. Murray. Structural changes in muscle crossbridges accompanying force generation. J. Cell Biol. 127: 763–778, 1994.
 131. Hobbs, L. W. Murphy's law and the uncertainty of electron probes. Scan. Microsc. Suppl. 4: 171–183, 1990.
 132. Holmes, K. C., D. Popp, W. Gebhard and W. Kabsch. Atomic model of the actin filament. Nature 347: 44–49, 1990.
 133. Holt, D. B. New directions in scanning electron microscopy cathodoluminescence microcharacterization. Scanning Microsc. 6: 1–21, 1992.
 134. Hoppe, W. and R. Hegerl. Three‐dimensional structure determination by electron microscopy (non‐periodic specimens). In Hawkes, P. W., ed., Computer Processing of Electron Microscope Images. Berlin: Springer Verlag, 1980: 127–186.
 135. Hopwood, D. and G. Milne. Fixation. In Harris, J. R. ed., Electron Microscopy in Biology: A Practical Approach. Oxford: Oxford University Press, 1991: 1–16.
 136. Horowits, R. and R. J. Pololsky. The positional stability of thick filaments in activated skeletal muscle depends on sarcomere length: evidence for the role of titin filaments. J. Cell Biol. 105: 2217–2223, 1987.
 137. Horowitz, A. K., K. Duggan, C. Buck, M. C. Geckerle and K. Burridge. Interaction of plasma membrane fibronectin receptor with talin—A transmembrane linkage. Nature 320: 531–33, 1986.
 138. Houmeida, A., J. Holt, L. Tskhovrebova and J. Trinick. Studies of the interaction between titin and myosin. J. Cell Biol. 131: 1471–1481, 1995.
 139. Huxley, H. E. and W. Brown. The low‐angle x‐ray diagram of vertebrate striated muscle and its behavior during contraction and rigor. J. Mol. Biol. 30: 383–434, 1967.
 140. Huxley, H. E., A. Stewart, H. Sosa and T. Irving. X‐ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. Biophys. J. 67: 2411–2421, 1994.
 141. Hyatt, A. D. Immunogold labeling techniques. In Harris, J. R. ed., Electron Microscopy in Biology: A Practical Approach. Oxford: Oxford University Press, 1991: 59–82.
 142. Irving, T. C., Li, Q., Williams, B. A., and B. M. Millman. Z/I and A‐band lattice spacings in frog skeletal muscle: effects of contraction and osmolarity. J. Musc. Res. Cell Motil. 19: 811–823, 1998.
 143. Isaacs, W. B., L. S. Kin, A. Struve and A. B. Fulton. Association of titin and myosin heavy chain in developing skeletal muscle. Proc. Natl. Acad. Sci. U.S.A., 89: 7496–7500, 1992.
 144. Jacobson, K., E. D. Sheets and R. Simson. Revisiting the fluid mosaic model of membranes. Science 268: 1441–1442, 1995.
 145. Jakubiec‐Puka, A., D. Frosch and R. Rudel. Ultrastructure of the contractile apparatus of rat skeletal muscle embedded in an aqueous medium. Gen. Physiol. Biophys. 8: 185–202, 1989.
 146. Jarosch, R. Muscle force arises by actin filament rotation and torque in the Z‐filaments. Biochem. Biophys. Res. Commun. 270 (3): 677–682, 2000.
 147. Jester, J. V., P. M. Andrews, W. M. Petroll, M. A. Lemp and H. D. Cavanagh. In vivo, real‐time confocal imaging. JEM Tech. 18: 50–60, 1991.
 148. Jin, J. P. Titin‐thin filament interaction and potential role in muscle function. Adv. Exp. Med. Biol. 481: 319–333, 2000.
 149. Johnson, D., K. Izutsu, M. Cantino, and J. Wong. High spatial resolution spectroscopy in the elemental microanalysis and imaging of biological systems, Ultramicroscopy 24: 221–235, 1988.
 150. Jordan, H. E. The structure of the heart muscle of the hummingbird with special reference to the intercalated discs. Anat. Rec. 5: 517–529, 1911.
 151. Jordan, H. E. The structural changes in striped muscle during contraction, Physiol. Rev. 13: 301–324, 1933.
 152. Joy, D. C. Beam interactions, contrast and resolution in the SEM. J. Microsc. 136: 241–258, 1984.
 153. Joy, D. C. and J. B. Pawley. High‐resolution scanning electron microscopy. Ultramicroscopy 47: 80–100, 1992.
 154. Karkoura, A., P. Tangkawattana, S. Yamano, K. Takehana, Y. Isumisawa, J. Masty and M. Yamaguchi. Hypertrophic Z‐line observed in aged one‐humped camel (Camelus dromedarius). Acta Anat. 153: 220–225, 1995.
 155. Katz, A. M. Physiology of the Heart. New York: Raven, 1992.
 156. Kaufmann, S., T. Piekenbrock, W. H. Goldmann, M. Barmann and G. Isenberg. Talin binds to actin and promotes filament nucleation. FEBS Lett 284: 187–191, 1991.
 157. Kawamura, Y., H. Kume, Y. Itoh, S. Ohtsuka, S. Kimura and K. Maruyuma. Localization of three fragments of connectin in chicken breast muscle sarcomeres. J. Biochem. 117: 201–207, 1995.
 158. Kelly, D. E. Models of muscle Z‐band fine structure based on a looping filament configuration. J. Cell Biol. 37: 507–520, 1967.
 159. Kelly, D. E. and M. A. Cahill. Filamentous and matrix components of skeletal muscle Z disks. Anat. Rec. 172: 623–642, 1972.
 160. Khan, M. A. An ultrastructural study of the stretch‐induced hypertrophy of skeletal muscle. Cell Biol. Int. 10: 955–962, 1986.
 161. King, M. V. Dimensional changes in cells and tissues during specimen preparation for the electron microscope. Cell Biophys. 18: 31–55, 1991.
 162. Kiss, J. Z. and L. A. Staehelin. High pressure freezing. In Severs, N. J. and D. M. Shotton, eds., Rapid Freezing, Freeze Fracture, and Deep Etching. New York: Wiley and Sons, 1995: 89–104.
 163. Knappeis, G. G. and R. Carlsen. The ultrastructure of the Z disc in skeletal muscle. J. Cell Biol. 13: 323–335, 1962.
 164. Kreis, T. and R. Vale. Guidebook to the Extracellular Matrix and Adhesion Proteins. New York: Oxford University Press, 1993.
 165. Kreis, T. and R. Vale. Guidebook to the Cytoskeletal and Motor Proteins. New York: Oxford University Press, 1993.
 166. Kuisk, I. R., H. Li, D. Tran and Y. Capetanaki. A single MEF2 site governs desmin transcription in both heart and skeletal muscle during mouse embryogenesis. Dev. Biol. 174: 1–13, 1996.
 167. Kuroda, M., T. Tanaka and T. Masaki. Eu‐actin, a new structural protein of the Z line of striated muscles. J. Biochem. 89: 297–310, 1981.
 168. Labeit, S., B. Kolmerer and W. A. Linke. The giant protein titin. Emerging roles in physiology and pathophysiology. Circ. Res. 80: 290–294, 1997.
 169. Lal, R. and S. A. John. Biological applications of atomic force microscopy. Am. J. Physiol. 266 (Cell Physiol. 35): C1–C21, 1994.
 170. Lal, R., S. A. John, D. W. Laird and M. F. Arnsdorf. Heart gap junctions preparations reveal hemiplaques by atomic force microscopy. Am. J. Physiol. 268 (Cell Physiol 37): C968–C977, 1995.
 171. Landon, D. N. Change in Z‐disc structure with muscular contraction. J. Physiol. (Lond.) 211: 44–45, 1970.
 172. Laurent, M., B. Johannin, N. Gilbert, L. Lucas, D. Cassio, P. X. Petit and A. Fleury. Power and limits of laser scanning confocal microscopy. Biol. Cell 80: 229–240, 1994.
 173. Lazarides, E. Intermediate filaments as mechanical integrators of cellular space. Nature 283: 247–256, 1980.
 174. Leapman, R. D. and S. B. Andrews. Analysis of directly frozen macromolecules and tissues in the field‐emission STEM. J. Microsc. 161: 3–19, 1991.
 175. Leeuwenhoek mentioned the transverse striations of muscle in his letters, as quoted by Bowman, 1840.
 176. Legato, M. J. Sarcomerogenesis in human myocardium. J. Mol. Cell. Cardiol. 1: 425–437, 1970.
 177. Linke, W. A., M. L. Bertoo and G. H. Pollack. Spontaneous sarcomeric oscillations at intermediate activation levels in single isolated cardiac myofibrils. Circ. Res. 73: 724–734, 1993.
 178. Linke, W. A. Stretching molecular springs: elasticity of titin filaments in vertebrate striated muscle. Histol. Histopathol. 15: 799–811, 2000.
 179. Linner, J. G., S. A. Livesay, D. S. Harrison and A. L. Steiner. A new technique for removal of amorphous phase tissue water without ice crystal damage: a preparative method for ultrastructural analysis and immunoelectron microscopy. J. Histochem. Cytochem. 34: 1123–1135, 1986.
 180. Liversage, A. D., D. Holmes, P. J. Knight, L. Tskhovrebova, J. Trinick. Titin and the Sarcomere Symmetry Paradox. J. Mol. Biol. 305: 401–409, 2001.
 181. Luft, J. H. Embedding media—old and new. In Koehler, J. H., ed., Advanced Techniques in Biological Electron Microscopy, New York: Springer‐Verlag, 1973: 1–34.
 182. Luna, E. J. and A. L. Hitt. Cytoskeleton–plasma membrane interactions. Science 258: 955–964, 1992.
 183. Luther, P. K. and J. M. Squire. Three‐dimensional structure of the vertebrate muscle A band. II. The myosin filament super‐lattice. J. Mol. Biol. 141: 409–439, 1980.
 184. Luther, P. K. and J. M. Squire. Three‐dimensional structure of the vertebrate muscle M‐region. J. Mol. Biol. 125: 313–324, 1978.
 185. Luther, P. K., M. C. Lawrence, and R. A. Crowther. A method for monitoring the collapse of plastic sections as a function of electron dose. Ultramicroscopy 24: 7–18, 1988.
 186. Luther, P. K. Three‐dimensional reconstruction of a simple Z‐band in fish muscle. J. Cell Biol. 113: 1043–1055, 1991.
 187. Luther, P. K., Sample shrinkage and radiation damage. In J. Frank, ed., Electron Tomography—Three‐Dimensional Imaging with the Transmission Electron Microscope, New York: Plenum, 1992: 39–60.
 188. Luther, P. K. Symmetry of a vertebrate muscle basketweave Z‐band. J. Struct. Biol. 115: 275–282, 1995.
 189. Luther, P. K. Three‐dimensional structure of a vertebrate muscle Z‐band: implications for titin and alpha‐actinin binding. J. Struct. Biol. 129: 1–16, 2000.
 190. Macagno, E. R., C. Levinthal and I. Sobel. Three‐dimensional computer reconstruction of neurons and neuronal assemblies. Annu. Rev. Biophys. Bioeng. 8: 323–351, 1979.
 191. MacDonald, N. C. Auger electron spectroscopy for scanning electron microscopy. Scanning Electron Microsc. 1971: 88–96, 1971.
 192. Maguruma, M., S. Matsumura and T. Fukazawa. Direct interaction between talin and actin. Biochem. Biophys. Res. Commun. 171: 1217–1223, 1990.
 193. Maher, P. A., G. F. Cox and S. J. Singer. Zeugmatin: a new high molecular weight protein associated with Z lines in adult and early embryonic striated muscle. J. Cell Biol. 101: 1871–1883, 1985.
 194. Marko, M., A. Leith and D. Parsons. Three‐dimensional reconstruction of cells from serial section and whole cell mounts using multilevel contouring of stereo micrographs. JEM Tech. 9: 395–412, 1988.
 195. Maron, B. J., V. J. Ferrans and W. C. Roberts. Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am. J. Pathol. 79: 387–434, 1975.
 196. Marti, O. SXM: an introduction. In Marti, O. and M. Amrein, eds., STM and SFM in Biology. New York: Academic, 1993: 78–88.
 197. Martin, W. D. Time course of change in soleus muscle fibers of rats subjected to chronic centrifugation. Aviat. Space Environ. Med. 49: 792–297, 1978.
 198. Maruyama, K., T. Endo, H. Kume, Y. Kawamura, N. Kanzawa, Y. Nakauchi, S. Kimura, S. Kawashima and K. Maruyama. A novel domain sequence of connectin localized at the I band of skeletal muscle sarcomeres: homology to neurofilament subunits. Biochem. Biophys. Res. Commun. 194: 1288–1291, 1993.
 199. Maruyama, K. Connectin, an elastic protein of striated muscle. Biophys. Chem. 50: 73–85, 1994.
 200. Matsubara, I. and B. M. Millman. X‐ray diffraction studies on cardiac muscle. In The Physiological Basis of Starling's Law of the Heart. Amsterdam: North‐Holland, 31–41, 1974.
 201. McDonald, K. L. Electron microscopy and EM immunocytochemistry. Meth. Cell Biol. 44 411–44, 1994.
 202. McDonald, K. A., M. Lakonishok and A. F. Horowitz. alpha‐v and alpha‐3 integrin subunits are associated with myofibrils during myofibrillogenesis. J. Cell Sci. 108: 975–983, 1995.
 203. McGough, A., M. Way and D. DeRosier. Determination of the alpha‐actinin site on actin filaments by cryoelectron microscopy and image analysis. J. Cell Biol. 126: 433–443, 1994.
 204. Meek, G. A. Practical Electron Microscopy for Biologists, 2nd Edition. New York: John Wiley & Sons, 1976: 81–83; 376–384; 414–415.
 205. Mellema, J. E. Computer reconstruction of regular biological objects. In Hawkes, P. W. ed., Computer Processing of Electron Microscope Images, Berlin: Springer Verlag, 1980: 89–126.
 206. Messerli, J. M. and J. C. Perriard. Three‐dimensional analysis and visualization of myofibrillogenesis in adult cardiomyocytes by confocal microscopy. Microsc. Res. Tech. 30: 521–30, 1995.
 207. Millevoi, S. K., Trombitas, B., Kolmerer, S., Kostin, J., Schaper, K., Pelin, H., Granzier, and S. Labeit. Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z‐discs. J. Mol. Biol. 282: 111–123, 1998.
 208. Milligan, R. A., M. Whittaker and D. Safer. Molecular structure of F‐actin and location of surface binding sites. Nature 348: 217–221, 1990.
 209. Milner, D. J., G. Weitzer, D. Tran, A. Bradley and Y. Capetanaki. Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J. Cell Biol. 134: 1255–1270, 1996.
 210. Misell, D. L. Image analysis, enhancement and interpretation. In A. M. Galauert, ed., Practical Methods in Electron Microscopy, Vol. 7. New York: North Holland, 1978: 125–197.
 211. Mohanty, S. B. Electron Microscopy for Biologists. Springfield, Il: Charles C. Thomas, 1982: 183.
 212. Mollenhauer, H. H. Artifacts caused by dehydration and epoxy embedding in transmission electron microscopy. Microsc. Res. Tech. 26: 496–512, 1993.
 213. Molony, L., D. McCaslin, J. Abernethy, B. Paschal and K. Burridge. Properties of talin from chicken gizzard smooth muscle. J. Biol. Chem. 262: 7790–7795, 1987.
 214. Moncman, C. L. and K. Wang. Nebulette: a 107 kD nebulinlike protein in cardiac muscle. Cell Motil. Cytoskel. 32: 205–225, 1995.
 215. Moncman, C. L. and K. Wang. Assembly of nebulin into the sarcomeres of avian skeletal muscle. Cell Motil. Cytoskel. 34: 167–84, 1996.
 216. Moncman, C. L. and K. Wang. Architecture of the thin filament‐z‐line junction lessons from nebulette and nebulin homologies. J. Musc. Res. Cell Motil. 21: 153–169, 2000.
 217. Mora, M., C. Di Blasi, R. Barresi, L. Morandi, B. Brambati, L. Jarre and F. Cornelio. Developmental expression of dystrophin, dystrophin‐associated glycoproteins and other membrane cytoskeletal proteins in human skeletal and heart muscle. Brain Res., 91: 70–82, 1996.
 218. Morris, E. P., G. Nneji and J. M. Squire. The three‐dimensional structure of the nemaline rod Z‐band. J. Cell Biol. 111: 2961–2978, 1990.
 219. Nassar, R., N. R. Wallace, I. Taylor and J. R. Sommer. The quick‐freezing of single intact skeletal muscle fibers at known time intervals following electrical stimulation. Scanning Electron Microsc. I: 309–328, 1986.
 220. Nave, R., D. O. Furst and K. Weber. Visualization of the polarity of isolated titin molecules: a single globular head on a long thin rod as the M band anchoring domain?. J. Cell Biol. 109: 2177–2187, 1989.
 221. Niggali, V., K. S. Kaufmann, W. H. Goldmann, T. Weber and G. Isenberg. Identification of functional domains in the cytoskeletal protein talin. Eur. J. Biochem. 227: 951–57, 1994.
 222. Noguchi, S., E. M. McNally, K. Ben Othmane, Y. Hagiwara, Y. Mizuno, M. Yoshida, H. Yamamoto, C. G. Bonnemann, E. Gussoni, P. H. Denton, et al. Mutations in the dystrophinassociated protein gamma‐sarcoglycan in chromosome 13 muscular dystrophy. Science 270: 819–822, 1995.
 223. Oberholzer, M., M. Ostreicher, H. Christen and M. Bruhlmann. Methods in quantitative image analysis. Histochem. Cell Biol. 105: 333–335, 1996.
 224. Obermann, W. M., M. Gautel, F. Steiner, P. F. van der Ven, K. Weber and D. O. Furst. The structure of the sarcomeric M band: localization of defined domains of myomesin, M‐protein, and the 250 kD corboxy‐terminal region of titin by immunoelectron microscopy. J. Cell Biol. 134: 1441–1453, 1996.
 225. Obermann, W. M., M. Gautel, K. Wever and D. O. Furst. Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin. EMBO J. 16: 211–220, 1997.
 226. Ohlendieck, I. Towards an understanding of the dystrophinglycoprotein complex: linkage between the extracellular matrix and the membrane cytoskeleton in muscle fibers. Eur. J. Cell Biol. 69: 1–10, 1996.
 227. Ohtsuka, H., H. Yajima, K. Maryune and S. Kimura. Binding of the N‐terminal 63 kDa portion of connectin/titin to alpha actinin as revealed by the yeast two‐hybrid system. FEBS Lett. 401: 65–67, 1997.
 228. Otto, J. J. Vinculin. Cell Motil. Cytoskel. 16: 1–6, 1990.
 229. Padron, R., L. Alamo, R. Craig and C. Caputo. A method for quick‐freezing live muscles at known instants during contraction with simultaneous recording of mechanical tension. J. Microsc. 151: 81–102, 1988.
 230. Padron, R., G. Maristela, L. Alamo, J. R. Guerrero and R. Craig. Visualization of myosin helices in sections of rapidly frozen relaxed tarantula muscle. J. Struct. Biol. 108: 269–276, 1992.
 231. Palmer, R. E. and K. P. Roos. Extent of radial sarcomere coupling revealed in passively stretched cardiac myocytes. Cell Motil. Cytoskel. 37: 378–388, 1997.
 232. Pameijer, C. H. Replica techniques for scanning electron microscopy—a review. In Becker, R. P. and O. Johari, eds., Scanning Electron Microscopy/1978/II., Scanning Electron Microscopy, Inc., AMF O'Hare, Illinois, 1978: 831–836.
 233. Papa, I. C. Astier, O. Kwiatek, F. Raynaud, C. Bonnal, M.‐C. Lebart, C. Roustan, and Y. Benyamin. Alpha actinin‐CapZ, an anchoring complex for thin filaments in Z‐line. J. Musc. Res. Cell Motil. 20: 187–197, 1999.
 234. Pardo, J. V., J. D. Siliciano and S. W. Craig. A vinculincontaining cortical lattice in skeletal muscle: transverse lattice elements (“costameres”) mark sites of attachment between myofibrils and sarcolemma. Proc. Natl. Acad. Sci. U.S.A. 80: 1008–1012, 1983.
 235. Pask, H. T., K. L. Jones, P. K. Luther and J. M. Squire. M‐band structure, M‐bridge interactions and contraction speed in vertebrate cardiac muscles. J. Musc. Res. Cell Motil. 15: 633–645, 1994.
 236. Pawley, J. B. Fundamental limits on confocal microscopy. In Pawley, J. B., ed., Handbook of Biological Confocal Microscopy, rev. ed. New York: Plenum, 1990: 15–26.
 237. Pawley, J. B., and S. L. Erlandsen. The case for low voltage high resolution scanning microscopy of biological samples. Scanning Microsc. Suppl. 3: 163–178, 1989.
 238. Peachey, L. D., and C. Franzini‐Armstrong. Structure and function of membrane systems of skeletal muscle cells. In Peachey, L. D., R. H. Adrian and S. R. Geiger, eds. Handbook of Physiology: Skeletal Muscle, Bethesda, MD: American Physiological Society, 1983: 23–71.
 239. Penczek, P., M. Radermacher and J. Frank. Three‐dimensional reconstruction of single particles embedded in ice. Ultramicroscopy 40: 33–53, 1992.
 240. Penman, S. Rethinking cell structure. Proc. Natl. Acad. Sci. U.S.A. 92: 5251–5257, 1995.
 241. Phillips, G. N., J. P. Fillers and C. Cohen. Tropomyosin crystal structure and muscle regulation. J. Mol. Biol. 192: 111–131, 1986.
 242. Polack, J. M. Monoclonal antibodies at the electron microscopical level. Int. J. Cancer Suppl. 2: 2–7, 1988.
 243. Pollack, G. H. Muscle contraction mechanism: are alternative engines gathering steam. Cardiovasc Res. 29: 737–746 (discussion 747–757), 1995.
 244. Pollack, G. H. Phase transitions and the molecular mechanism of contraction. Biophys. Chem. 59: 315–328, 1996.
 245. Price, M. Striated muscle endosarcomeric and exosarcomeric lattices. In: Malhotic, S. K., ed. Advances in Structural Biology Vol. 1. Greenwich, CT: Jo's Press, 1990: 175–207.
 246. Price, M. G. and R. H. Gomer. Skelemin, a cytoskeletal M‐disc periphery protein, contains motifs of adhesion/recognition and intermediate filament proteins. J. Biol. Chem. 268: 21800–21810, 1993.
 247. Price, M. G. and E. Lazarides. Expression of intermediate filament‐associated proteins paranemin and synemin in chicken development. J. Cell Biol. 97: 1860–1874, 1983.
 248. Radermacher, M. Weighted back‐projection methods. In Frank, J. ed., Electron Tomography—three‐dimensional imaging with the transmission electron microscope. New York: Plenum, 1992: 91–116.
 249. Radermacher, M. Three‐dimensional reconstruction of single particles from random and nonrandom tilt series. JEM Tech. 9: 359–394, 1988.
 250. Rappaport, L. and J. L. Samuel. Microtubules in cardiac myocytes. Int. Rev. Cytol. 113: 101–143, 1988.
 251. Rayment, I. R. R. Wojciech, K. Schmidt‐Base, R. Smith, D. R. Tomchick, M. M. Benning, D. A. Winkelmann, G. Wesenberg, and H. M. Holden. Three‐dimensional structure of myosin subfragment‐1: a molecular motor. Science 261: 50–57, 1993.
 252. Rayment, I., H. M. Holden, M. Whittaker, C. B. Yohn, M. Lorenz, K. C. Holmes and R. A. Milligan. Structure of the actinmyosin complex and its implications for muscle contraction. Science 261: 58–65, 1993.
 253. Reddy, M. K., J. D. Etlinger, M. Rabinowitz, D. A. Fischman and R. Zak. Removal of Z lines and alpha‐actinin from isolated myofibrils by a calcium activated neutral protease. J. Biol. Chem. 250: 4278–4284, 1975.
 254. Reedy, M. K. The structure of actin filaments and the origin of the axial periodicity in the I substance of vertebrate striated muscle. Proc. R. Soc. Lond. B 160: 458–460, 1964.
 255. Reith, A. and T. M. Mayhew. Stereology and Morphology in Electron Microscopy—Problems and Solutions. New York: Hemisphere Publishing, 1988.
 256. Riley, D. A., S. Ellis, C. S. Giometti, J. F. Y. Hoh, E. I. Ilyina‐Kakueva, V. A. Oganov, G. R. Slocum, J. L. W. Gain and F. R. Sedlak. Muscle sarcomere lesions and thrombosis after spaceflight and suspension loading. J. Appl Physiol. 73 (Suppl.): 33S–43S, 1992.
 257. Robinson, T. F. and S. Winegrad. The measurement and dynamic implications of thin filament lengths in heart muscle. J. Physiol. 286: 607–619, 1979.
 258. Robinson, T. F. Lateral connections between heart muscle cells as revealed by conventional and high voltage transmission electron microscopy. Cell Tissue Res. 211: 353–359, 1980.
 259. Robinson, T. F. and S. Winegrad. A variety of intercellular connections in heart muscle. J. Mol. Cell Cardiol. 13: 185–195, 1981.
 260. Robinson, T. F., L. Cohen‐Gould and S. M. Factor. Skeletal framework of mammalian heart muscle: arrangement of interand pericellular connective tissue structures. Lab. Invest. 49: 482–498, 1983.
 261. Robinson, T. F., S. M. Factor, J. M. Capasso, B. A. Wittenberg, O. O. Blumefeld and S. Seifter. Morphology, composition, and function of struts between cardiac myocytes of rat and hamster. Cell Tissue Res. 249: 247–255, 1987.
 262. Robinson, D. G., U. Ehlers, R. Herken, B. Herrman, F. Mayer and F.‐W. Shurmann. Methods of Preparation for Electron Microscopy—An Introduction for the Biomedical Sciences. Berlin: Springer‐Verlag, 1987: 24.
 263. Robinson, V. N. E. Materials characterization using the backscattered electron signal in scanning electron microscopy. Scanning Microsc. 1: 107–117, 1987.
 264. Roos, N. Freeze‐substitution and other low temperature embedding methods. In Harris, J. R. ed., Electron Microscopy in Biology: A Practical Approach. Oxford: Oxford University Press, 1991: 39–58.
 265. Rosenbloom, J., W. R. Abrams and R. Mechan. Extracellular matrix 4: the elastic fiber. FASEB J. 7: 1208–1218, 1993.
 266. Roth, J. Post‐embedding cytochemistry with gold labelled reagents: a review. J. Microsc. 143 (Pt 2): 125–137, 1986.
 267. Roth, J. The silver anniversary of gold: 25 years of the colloidal gold marker system for immunocytochemistry and histochemistry. Histochem. Cell Biol. 106: 1–8, 1996.
 268. Rowe, R. W. D. The ultrastructure of the Z discs from white, intermediate, and red fibres of mammalian striated muscles. J. Cell Biol. 57: 261–277, 1973.
 269. Ruiz, T., I. Erk and J. Lepault. Electron cryo‐microscopy of vitrified biological specimens: towards high spatial and temporal resolution. Biol. Cell 80: 203–210, 1994.
 270. Saide, J. D. and W. C. Ullrick. Fine structure of the honeybee Z disk. J. Mol. Biol. 79: 329–377, 1973.
 271. Sanger, J. M., B. Mittal, M. B. Pochapin and J. W. Sanger. Myofibrillogenesis in living cells microinjected with fluorescently labeled alpha‐actinin. J. Cell Biol. 102: 2053–2066, 1986.
 272. Saxton, W. D. and W. Baumeister. The correlation averaging of a regularly arranged bacterial cell envelope protein. J. Microsc. 127: 127–138, 1982.
 273. Schachat, F. H., A. C. Canine, M. M. Brigs, and M. C. Reedy. The presence of two skeletal muscle alpha‐actinins correlates with troponin‐tropomyosin expression and Z‐line width. J. Cell Biol. 101: 1001–1008, 1985.
 274. Schafer, D. A., J. A. Waddle and J. A. Cooper. Localization of CapZ during myofibrillogenesis in cultured chicken muscle. Cell Motil. Cytoskel. 25: 317–335, 1993.
 275. Schafer, D. A., C. Hug and J. A. Cooper. Inhibition of CapZ during myofibrillogenesis alters assembly of actin filaments. J. Cell Biol. 128: 61–70, 1995.
 276. Schaper J. R. Froede, S. Hein, A. Buck, H. Hashizume, B. Speiser, A. Friedl and N. Bleese. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 83: 504–514, 1991.
 277. Schollmeyer, J. V., D. E. Goll, M. H. Stromer, W. Dayton, I. Singh and R. Robson. Studies on the composition of the Z‐disk. J. Cell Biol. 63: 303a, 1974.
 278. Schroeter, J. P., J.‐P. Bretaudiere and M. A. Goldstein. Similar features in Z bands of both skeletal and cardiac muscle revealed by image enhancement. JEM Tech. 18: 296–304, 1991.
 279. Schroeter, J. P., J.‐P. Bretaudiere, R. L. Sass and M. A. Goldstein. Three‐dimensional structure of the Z band in a normal mammalian skeletal muscle. J. Cell Biol. 133: 571–583, 1996.
 280. Schultheiss, T., J. Choi, Z. X. Lin, C. Dilullo, L. Cohen‐Gould, D. Fischman and H. Holtzer. A sarcomeric alpha‐actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline‐line bodies and breakdown of myofibrils in myotubes. Proc. Natl. Acad. Sci. U.S.A. 89: 9282–9286, 1992.
 281. Shear, C. R. and R. J. Bloch. Vinculin in subsarcolemmal densities. J. Cell Biol. 101: 240–256, 1985.
 282. Shy, G. M., W. K. Engel, J. E. Somers and T. Wanko. Nemaline myopathy. A new congenital myopathy. Brain 86: 793–810, 1963.
 283. Sjostrom, M., J. M. Squire, P. Luther, E. Morris and A. C. Edman. Cryoultramicrotomy of muscle: improved preservation and resolution of muscle ultrastructure using negatively stained ultrathin cryosections. J. Microsc. 163 (Pt 1): 29–42, 1991.
 284. Small, J. V., D. O. Furst and L.‐E. Thornell. The cytoskeletal lattice of muscle cells. Eur. J. Biochem. 208: 559–572, 1992.
 285. Smith, M. and S. Croft. Embedding and thin section preparation. In Harris, J. R. ed., Electron Microscopy in Biology: A Practical Approach. Oxford: Oxford University Press, 1991: 17–37.
 286. Sommer, J. R. and R. B. Jennings. Ultrastructure of mammalian cardiac muscle. In Fozzard, H. A., ed., The Heart and Cardiovascular System. New York: Raven, 1986: 61–100.
 287. Sommer, J. R. and E. A. Johnson. Ultrastructure of cardiac muscle. In Berne, R. A. and N. Sperelakis, eds., The Handbook of Physiology—The Cardiovascular System, vol 2. Baltimore: American Physiological Society, 1980: 113–186.
 288. Sommer, J. R., E. A. Johnson, N. R. Wallace and R. Nassar. Cardiac muscle following quick‐freezing: preservation of in vivo ultrastructure and geometry with special emphasis on intracellular clefts in the intact frog heart. J. Mol. Cell Cardiol. 20: 285–302, 1988.
 289. Sommer, J. R. and R. A. Waugh. The ultrastructure of the mammalian cardiac muscle cell, with special emphasis on the tubular membrane systems. A review. Am. J. Pathol. 82: 192–232, 1976.
 290. Stelzer, E. H. K. and R. W. Wijnaendts‐van‐Resand. Optical cell splicing with the confocal fluorescence microscope: Microtomoscopy. In Wilson, T., ed., Confocal Microscopy, New York: Academic Press, 1990: 199–212.
 291. Stevenson, S., S. Rothery, M. J. Cullen and N. J. Severs. Dystrophin is not a specific component of the cardiac costamere. Circ. Res. 80: 269–280, 1997.
 292. Stewart, M. Transmission electron microscopy of frozen hydrated biological material. Elec. Microsc. Rev. 2: 117–121, 1989.
 293. Stewart, M. Introduction to the computer image processing of electron micrographs of two dimensionally ordered biological structures. JEM Tech. 9: 301–324, 1988.
 294. Stoker, M. E., A. M. Gerdes and J. F. May. Regional differences in capillary density and myocyte size in the normal human heart. Anat. Rec. 202: 187–191, 1982.
 295. Stromer, M. H. and D. E. Goll. Studies on purified alphaactinin. II. Electron microscopic studies on the competitive binding of alpha‐actinin and tropomyosin to Z‐line extracted myofibrils. J. Mol. Biol. 67: 489–494, 1972.
 296. Stromer, M. H. Immunocytochemical localization of proteins in striated muscle. Int. Rev. Cytol. 142: 61–144, 1992.
 297. Stromer, M. H. Immunocytochemistry of the muscle cell cytoskeleton. Microsc. Res. Tech. 31: 95–105, 1995.
 298. Takahashi, K., A. Hattori, R. Tatsumi and K. Takai. Calciuminduced splitting of connectin filaments into beta‐connectin and a 1,200 kDa subfragment. J. Biochem. 111: 778–782, 1992.
 299. Tameyasu, T., N. Ishide and G. H. Pollack. Discrete sarcomere length distribution in skeletal muscle. Biophys. J. 37: 489–492, 1982.
 300. Tangkawattana, P., A. Karkoura, M. Muto, S. Yamano, H. Taniyama and M. Yamaguchi. Cardiac rod body: hypertrophic Zline in an aged pony. Acta Anat. 155: 266–273, 1996.
 301. Taylor, K. A. and D. W. Taylor. Formation of two‐dimensional complexes of F‐actin and crosslinking proteins on lipid monolayers: demonstration of unipolar alpha‐actinin‐F‐actin crosslinking. Biophys. J. 67: 1976–1983, 1994.
 302. Thomason, D. B., P. R. Morrison, V. Oganov, E. Ilyina‐Kakueva, F. W. Booth and K. M. Baldwin. Altered actin and myosin expression in muscle during exposure to microgravity. J. Appl. Physiol. 73 (Suppl.): 90S–93S, 1992.
 303. Thornell, L.‐E. and M. G. Price. The cytoskeleton in muscle cells in relation to function. Biochem. Soc. Trans. 19: 1116–1120, 1991.
 304. Tidball, J. G., T. O'Halloran and K. Burridge. Talin at myotendinous junctions. J. Cell Biol. 103: 1465–1472, 1986.
 305. Tidball, J. G. and K. L. Andolina. Structure and protein composition of sites of papillary muscle attachment to chordae tendineae in avian hearts. Cell Tissue Res. 270: 527–533, 1992.
 306. Tirion, M. M., D. ben‐Avraham, M. Lorenz and K. C. Holmes. Normal modes as refinement parameters for the F‐actin model. Biophys. J. 68: 5–12, 1995.
 307. Tokuyasu, K. T., A. H. Dutton, B. Geiger and S. J. Singer. Ultrastructure of chicken cardiac muscle as studied by double immunolabeling in electron microscopy. Proc. Natl. Acad. Sci. U.S.A. 78: 7619–7623, 1981.
 308. Tokuyasu, K. T., A. H. Dutton and S. J. Singer. Immunoelectron microscopic studies of desmin (skeletin) localization and intermediate filament organization in chicken cardiac muscle. J. Cell Biol. 96: 1736–1742, 1983.
 309. Tokuyasu, K. T., P. A. Maher, and S. J. Singer. Distributions of vimentin and desmin in developing chick myotubes in vivo. II. Immunoelectron microscopic study. J. Cell Biol. 100: 1157–1166, 1985.
 310. Traeger, L. A. and M. A. Goldstein. Thin filaments are not of uniform length in rat skeletal muscle. J. Cell Biol. 96: 100–103, 1983.
 311. Trinick, J. Understanding the functions of titin and nebulin. FEBS Lett. 307: 44–48, 1992.
 312. Trombitas, K., G. H. Pollack, J. Wright and K. Wang. Elastic properties of titin filaments demonstrated using a “freezebreak” technique. Cell Motil. Cytoskel. 24: 274–283, 1993.
 313. Trombitas, K. and G. H. Pollack. Elastic properties of the titin filament in the Z‐line region of vertebrate striated muscle. J. Musc. Res. Cell Motil. 14: 416–422, 1993.
 314. Trombitas, K. and G. H. Pollack. Elastic properties of connecting filaments along the sarcomere. Adv. Exp. Med. Biol. 332 71–79, 1993.
 315. Trombitas, K. K., A. Redkar, T. Centner, Y. Wu, S. Labeit, and H. Granzier. Extensibility of isoforms of cardiac titin: variation in contour length of molecular subsegments provides a basis for cellular passive stiffness diversity. Biophys. J. 79: 3226–3234, 2000.
 316. Truex, R. C. Myocardial cell diameters in primate hearts. Am. J. Anat., 135: 269–280, 1972.
 317. Turnacioglu, K. K., B. Mittal, J. M. Sanger and J. W. Sanger. Partial characterization of zeugmatin indicates that it is part of the Z‐band region of titin. Cell Motil. Cytoskel. 34: 108–121, 1996.
 318. Turnacioglu, K. K. B. Mittal, G. A. Dabiri, J. M. Sanger, and J. W. Sanger. Zeugmatin is part of the Z‐band targeting region of titin. Cell Struct. Funct. 22: 73–82, 1997.
 319. Ullrick, W. C., P. A. Toselli, J. D. Saide and W. P. C. Phear. Fine structure of the vertebrate Z‐disc. J. Mol. Biol. 115: 61–74, 1977.
 320. Van Der Ven, P. F., Oberman, W. M., Lemke, B., Gautel, M., Weber, K. and Furst, D. O. Characterization of muscle filamin isoforms suggests a possible role of gamma‐filamin/ABP‐L in sarcomeric Z‐disc formation. Cell Motil. Cytoskel. 45: 149–162, 2000.
 321. Van Der Ven, P. F., Obermann, W. M., K. Weber, and D. O. Furst. Myomesin, M‐protein and the structure of the sarcomeric M‐band. Adv. Biophys. 33: 91–99, 1996.
 322. Vanderloop, F., G. Schaart, W. Langmann, F. Ramaekers and C. Viebahn. Expression and organization of muscle specific proteins during the early developmental stages of the rabbit heart. Anat. Embryol. 185: 439–450, 1992.
 323. Vigoreaux, J. O. The muscle Z band: lessons in stress management. J. Musc. Res. Cell Motil. 15: 237–255, 1994.
 324. Vinkemeier, U., W. Obermann, K. Weber and D. O. Furst. The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin‐associated proteins. J. Cell Sci. 106: 319–330, 1993.
 325. von Palczewska, I., Uber die Struktur der menschlichen Herzmuskelfasern. Arch. fur Mikros. Anat. 41–100, 1910.
 326. Wade, J. B., W. A. Kachadorian and V. A. DiScala. Freezefracture electron microscopy: relationship of membrane features to transport physiology. Am. J. Physiol. 232 (Renal Fluid Electrolyte Physiol. 1): F77–83, 1977.
 327. Wakabayashi, K., Y. Sugimoto, H. Tanaka, Y. Ueno, Y. Takezawa and Y. Amemiya. X‐ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction. Biophys. J. 67: 2422–435, 1994.
 328. Wall, J. S., J. F. Hainfeld, P. A. Bartlett and S. J. Singer. Observation of an undecagold cluster compound in the scanning transmission electron microscope. Ultramicroscopy 8: 397–402, 1982.
 329. Wallgren‐Pettersson, C., B. Jasani, G. R. Newman, G. E. Morris, S. Jones, S. Singhrao, A. Clarke, I. Virtanen, C. Holmberg and J. Rapola. Alpha‐actinin in nemaline bodies in congenital nemaline myopathy: immunological confirmation by light and electron microscopy. Neuromuscal. Disord. 5: 93–104, 1995.
 330. Wallimann, T., T. C. Doetschman and H. M. Eppenberger. Novel staining pattern of skeletal muscle M‐lines upon incubation with antibodies against creatine kinase. J. Cell Biol. 96: 1772–1779, 1983.
 331. Wang, K. and R. Ramirez‐Mitchell. A network of transverse and longitudinal intermediate filaments is associated with sarcomeres of adult vertebrate skeletal muscle. J. Cell Biol. 96: 562–570, 1983.
 332. Wang, K., R. McCarter, J. Wright, J. Beverly and R. Ramirez‐Mitchell. Viscoelasticity of the sarcomere matrix of skeletal muscles. The titin‐myosin composite filament is a dual stage molecular spring. Biophys. J. 64: 1161–1177, 1993.
 333. Wang, K. Titin/connectin and nebulin: giant protein rulers of muscle structure and function. Adv. Biophys. 33: 123–134, 1996.
 334. Wang, L., M. M. Rahman, H. Iida, T. Inai, S. Kawabata, S. Iwanaga and Y. Shibata. Annexin V is localized in association with Z‐line of rat cardiac myocytes. Cardiovasc. Res. 30: 363–371, 1995.
 335. Wang, S. M., C. J. Jeng and M. C. Sun. Studies on the interaction between titin and myosin. Histol. Histopathol. 7: 333–337, 1992.
 336. Weakley, B. S. A Beginner's Handbook in Biological Transmission Electron Microscopy. London: Churchill Livingstone, 1981: 62–63; 142–144.
 337. Welland, M. E. and M. E. Taylor. Scanning tunneling microscopy. In Duke, P. J. and A. J. Michette, eds., Modern Microscopies—Techniques and Applications. New York: Plenum, 1990: 231–254.
 338. Whiting, A., J. Wardale and J. Trinick. Does titin regulate the length of muscle thick filaments?. J. Mol. Biol. 205: 263–268, 1989.
 339. Williams, R. C. and H. W. Fisher. Electron microscopy of tobacco mosaic virus under conditions of minimal beam exposure. J. Mol. Biol. 52: 121–123, 1970.
 340. Winkler, J., H. Lunsdorf and B. M. Jockusch. Energy filtered electron microscopy reveals that talin is a highly flexible protein composed of a series of globular domains. Eur. J. Biochem. 243: 430–436, 1997.
 341. Worton, R. Muscular dystrophies: diseases of the dystrophinglycoprotein complex. Science 270: 755–756, 1995.
 342. Wright, J., Q. Q. Huang and K. Wang. Nebulin is a full‐length template of actin filaments in the skeletal muscle sarcomere: an immunoelectron microscopic study of its orientation and span with site‐specific monoclonal antibodies. J. Musc. Res. Cell Motil. 14: 476–83, 1993.
 343. Yamaguchi, M., R. M. Robson, M. H. Stromer, D. S. Dahl and T. Oda. Actin filaments form the backbone of nemaline myopathy rods. Nature 271: 265–267, 1978.
 344. Yamaguchi, M., R. M. Robson and M. H. Stromer. Evidence for actin involvement in cardiac Z‐lines and Z‐line analogs. J. Cell Biol. 96: 435–442, 1983.
 345. Yamaguchi, M., R. M. Robson, M. H. Stromer, N. R. Cholvin and M. Izumimoto. Properties of soleus muscle Z‐lines and induced Z‐line analogs revealed by dissection with Ca2+‐activated neutral protease. Anat. Rec. 206: 345–362, 1983.
 346. Yamaguchi, M., M. Izumimoto, R. M. Robson and M. H. Stromer. Fine structure of wide and narrow vertebrate muscle Z lines. J. Mol. Biol. 184: 621–644, 1985.
 347. Yamaguchi, M., G. A. Fuller, W. Klomkleaw, S. Yamano, T. Oba. Z‐line structural diversity in frog single muscle fiber in the passive state. J. Musc. Res. Cell Motil. 20: 371–381, 1999.
 348. Yarom, R. and U. Meiri. N lines in striated muscle: a site of intracellular Ca2+. Nature [New Biol.] 234: 254–256, 1971.
 349. Young, P. C., Ferguson, S., Banuelos, and M. Gautel. Molecular structure of the sarcomeric Z‐disk: two types of titin interactions lead to a asymmetrical sorting of alpha‐actinin. EMBO J. 17: 1614–1624, 1998.
 350. Young, P. and M. Gautel. The interaction of titin and alphaactinin is controlled by a phospholipid‐regulated intramolecular pseudoligand mechanism. EMBO J. 19: 6331–6340, 2000.
 351. Yu, L. C., R. W. Lymn and R. J. Podolsky. Characterization of a non‐indexible equatorial x‐ray reflection from frog sartorius muscle. J. Mol. Biol. 115: 455–464, 1977.
 352. Yu, L. C. Analysis of equatorial x‐ray diffraction patterns from skeletal muscle. Biophys. J. 55: 433–440, 1989.
 353. Yung, R. and J. S. Frank. Extracellular matrix‐sarcolemmal surface interconnections: a quick‐freeze deep‐etch study. J. Ultrastruct. Mol. Struct. Res. 96: 160–171, 1986.
 354. Zierold, K. Preparation and transfer of ultrathin frozenhydrated and freeze‐dried cryosections for microanalysis in scanning transmission electron microscopy. Scanning Elec. Microsc. (Pt 3): 1205–1214, 1982.
 355. Zimmer, D. B. and M. A. Goldstein. Immunolocalization of alpha‐actinin in adult chicken skeletal muscles. JEM Tech. 6: 357–366, 1987.

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Margaret Ann Goldstein, John P. Schroeter. Ultrastructure of the Heart. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 3-74. First published in print 2002. doi: 10.1002/cphy.cp020101