Comprehensive Physiology Wiley Online Library

Ultrastructure of the Heart

Full Article on Wiley Online Library



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) .

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 .

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 ). 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 .

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) .

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) .

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 . 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 .

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) .

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) .

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) .

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 .

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 .

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 .

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 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 and 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 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 .

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 .

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 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 .

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 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 , 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 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 . The A‐band length is 1.56 μm. The 17 nm 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 , and . 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 .

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 .

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) .

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 and ; 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 and . 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 ; 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) .

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 .

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 ). 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 .

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) .

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) .

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 . 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 .

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) .

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) .

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) .

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 .

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 .

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 .

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 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 and 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 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 .

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 .

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 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 .

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 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 , 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 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 . The A‐band length is 1.56 μm. The 17 nm 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 , and . 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 .

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 .

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) .

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 and ; 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 and . 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 ; 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.

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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