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5 Muscle JO ANN EURELL Smooth Muscle...

5 Muscle JO ANN EURELL Smooth Muscle Classification of Skeletal Muscle Fibers Light Microscopic Structure Myogenesis, Hypertrophy, Atrophy, and Regeneration Fine Structure Cardiac Muscle Contraction Light Microscopic Structure Myogenesis, Hypertrophy, and Regeneration Fine Structure Skeletal Muscle Cardiac Nodes and Impulse Conduction Fibers Light Microscopic Structure Contraction Fine Structure Myogenesis, Hypertrophy, and Regeneration Contraction Many cells in the body are capable of contraction and limited longitudinally sectioned fibers. Other muscular tissue in the movement, but only specialized collections of cells known as mus- walls of hollow organs is composed of myocytes without cross- cle are capable of strong, concerted contraction to produce inte- striations and hence has a smooth appearance. Therefore, three grated movement. Muscular tissues are present in three principal basic types of muscle fibers are recognized: (1) nonstriated smooth areas of the vertebrate body: the walls of hollow organs (e.g., vis- muscle, which forms the contractile portion of the walls of most cera of the gastrointestinal tract, urogenital tract, blood vessels), viscera; (2) striated skeletal muscle, which comprises the skele- the skeletal muscles, and the heart. tal muscles that originate and insert on the bones of the skele- The specialized cells of muscular tissues have distinct mor- ton; and (3) striated cardiac muscle, which is the major tissue phologic characteristics directly related to their contractile acti- of the walls of the heart. Skeletal muscle is considered to be vol- vity. Muscle cells, also known as myocytes or myofibers, are untary in control, whereas cardiac muscle and smooth muscle are elongated cells with spindle-shaped or fiberlike profiles. The term involuntary. fiber in association with muscle refers to cells, in contrast to con- nective tissue fibers, which are condensed extracellular substances dispersed between cells. The myocytes are arranged in bundles with their long axes SMOOTH MUSCLE aligned parallel to the direction of their contractions. The shape Light Microscopic Structure of the profiles of myocytes is dependent on the angle of sec- tioning. Myocytes sectioned parallel to their long axes appear Smooth muscle cells are elongated, spindle-shaped cells (Fig. 5-1). as long rods or spindles, whereas those sectioned at right angles Each cell contains a single, centrally located nucleus. The cells are polygonal. Oblique sectioning results in various elliptic range from 5 to 20 µm in diameter and from 20 µm to 1 mm or profiles. more in length. The cytoplasm of smooth myocytes is acidophilic. Within the cytoplasm of all myocytes are abundant fibrous Within a tissue section, the cross-sectional size of cells is proteins that stain intensely eosinophilic. The arrangement of highly variable due to the tapered shape of the cells. Many cross these fibrous proteins is highly ordered in skeletal and cardiac sections of the cell lack nuclear profiles because of the extent of muscular tissue, resulting in characteristic cross-striations of the cell beyond the central nuclear region (Fig. 5-1A). 79 80 Dellmann’s Textbook of Veterinary Histology Contraction The contractile apparatus of smooth muscle is capable of greater shortening in length and more sustained contractions than that of striated muscle. Contraction is governed by the phosphorylation of the myosin-II molecule in contrast to striated muscle, which is regulated by a troponin–tropomyosin complex described below. The contraction sequence begins with an increase of cal- cium in the smooth muscle cell cytoplasm. Calcium increases by entering the cell through voltage-dependent calcium channels in the cell membrane or by inositol 1,4,5-triphosphate (IP3)- induced release of calcium from the smooth endoplasmic reticu- lum. The rise in cytosolic calcium leads to subsequent binding of the calcium to calmodulin. The calcium–calmodulin com- plex then interacts with myosin light-chain kinase, which ini- tiates phosphorylation of myosin-II and interaction between the actin and myosin-II myofilaments. The overall process leading to actin–myosin interaction is longer when compared with other muscle types, which results in the relatively slow contraction of FIGURE 5-1 Smooth muscle. A. Cross section. B. Longitudinal smooth muscle. section. The central myocyte nuclei (solid arrows) are absent in several cross sections due to sectional geometry. The tip of a Hormones that act via cyclic adenosine monophosphate spindle-shaped cell is visible at the dotted arrow. Fibroblast nuclei (cAMP) can affect smooth muscle contraction. cAMP activates (open arrow) are dark and smaller than smooth muscle nuclei. myosin light-chain kinase, leading to phosphorylation of myosin Hematoxylin and eosin (×490). and cell contraction. Estrogen increases cAMP and subsequently smooth muscle contraction, while progesterone decreases cAMP, resulting in decreased smooth muscle contraction. Individual myocytes are surrounded by a fine network of re- Contraction of smooth muscle is involuntary. Innervation is ticular fibers, blood vessels, and nerves. In smooth muscle, retic- both parasympathetic and sympathetic, and the effects of neural ular fibers are produced by myocytes rather than fibroblasts. input on smooth muscle are variable. Unitary smooth muscle, Although the connective tissue is analogous to the endomysium found in the wall of visceral organs, behaves as a syncytium that of skeletal muscle described below, it is not termed as such. contracts in a networked fashion. Cells of this arrangement of smooth muscle are extensively connected by gap junctions but sparsely innervated. In contrast, multiunit smooth muscle, Fine Structure found in the iris of the eye, is capable of precise contractions due The cytoplasm of the smooth muscle myocyte contains numer- to individual innervation of each myocyte. The multiunit myo- ous myofilaments in various orientations (Figs. 5-2 and 5-3). cytes lack gap junctions, resulting in reduced coordinated com- Thin myofilaments of smooth muscle contain actin and tropo- munication between cells. myosin but lack troponin, which is present in skeletal and car- diac muscle. Thick myofilaments, composed of myosin-II, are Myogenesis, Hypertrophy, sparse. The thick and thin myofilaments are not arranged in a and Regeneration highly ordered pattern as in striated muscle. Dense bodies in the cytoplasm and the cell membrane serve as anchor sites for the Smooth muscle tissue increases in size by both hypertrophy (in- myofilaments. Intermediate filaments (desmin and vimentin) crease in size) and hyperplasia (increase in number) of myocytes. further link the dense bodies into a meshwork array. The myofila- New smooth muscle cells can form through mitosis or by deri- ment attachment sites on the cell membrane also form junctions vation from pericytes. Formation of new myocytes is limited, so that connect adjacent cells. healing of smooth muscle is mainly through connective tissue Numerous pear-shaped invaginations (caveolae) and vesicles scar formation. are present along the cell membrane and are believed to play a role in calcium transport (Figs. 5-2 and 5-3). Transverse T tubules found in striated muscle are lacking and smooth endoplasmic SKELETAL MUSCLE reticulum is sparse. Gap junctions, which allow for cell coupling, occur at frequent periodic sites in the cell membrane. Other cel- Light Microscopic Structure lular organelles, including mitochondria, Golgi complex, rough Skeletal muscle myocytes are elongated cells that range from 10 endoplasmic reticulum (rER), and free ribosomes, are located near to 110 µm in diameter and can reach up to 50 cm in length. These the nucleus. Each myocyte is surrounded by a basal lamina, except fibers are derived from the prenatal fusion of many individual at intercellular junctions (Fig. 5-3). mononuclear myoblasts. As a result of the fusion, a single myocyte  Muscle Jo Ann Eurell 81 gap junction myofilament caveolae dense bodies FIGURE 5-2 The smooth muscle cell has a centrally located nucleus surrounded by cytoplasm containing myofilaments in various orientations. The contractile myofilaments anchor into dense bodies on the cell membrane and within the cytoplasm of the smooth muscle cell. When the myofilaments contract, the cell shortens (lower diagram). Numerous caveolae, vesicles, and gap junctions are present along the cell membrane. 82 Dellmann’s Textbook of Veterinary Histology FIGURE 5-4 Skeletal muscle, longitudinal section. Notice the cross-striations and the nuclei located in the periphery of the myocytes. Hematoxylin and eosin (×435). are responsible for contraction. The myofibrils align in a longitu- dinal direction to create the light and dark banding pattern of the myocyte. Thick and thin myofilaments overlap in the darker A band (anisotropic), whereas only thin myofilaments are present in the lighter I band (isotropic). The myofibrils are connected by in- termediate filaments of desmin and vimentin, such that the light and dark bands of all myofibrils within a fiber are in register. Satellite cells are spindle-shaped cells located adjacent to the cell membrane of the myocyte and within its basement mem- brane. Their nuclei are heterochromatic in contrast to the lighter- staining nuclei of the myocyte. Satellite cells are best recognized with electron microscopy. They are thought to represent a popu- lation of inactive myoblasts, which can be activated upon injury to initiate regeneration of muscle fibers. FIGURE 5-3 Electron micrograph of a cross-sectioned smooth muscle cell. The nucleus (N) is centrally located, and the cytoplasm contains numerous myofilaments. Electron-dense bodies (*) serve as attachment sites for the myofilaments. Numerous caveolae (arrowheads) are present along the plasma membrane of an adjacent cell. The basal laminae (L) are visible between the two cells and appear fused at points (×23,900). (Courtesy of W. S. Tyler.) contains multiple oval nuclei, which are peripherally located within the cell (Fig. 5-4). When viewed in longitudinal section, trans- verse striations are present as alternating light and dark bands. In transverse section, the myocyte has an angular outline and a stip- pled cytoplasm (Fig. 5-5). Peripheral nuclei may be absent in some planes of the cross section of the myocyte. The surrounding cell membrane is visible at higher magnification. Each muscle cell contains myofibrils, which form the dots in cross sections of the fiber at the light microscopic level (Fig. 5-6). FIGURE 5-5 Skeletal muscle, cross section. The nuclei in the The myofibrils are cylindrical and 1 to 2 µm in diameter. Individual sparse endomysium (arrows) belong to either fibroblasts or satellite myofibrils are composed of thick and thin myofilaments, which cells. Hematoxylin and eosin (×435).  Muscle Jo Ann Eurell 83 endomysium T tubules sarcolemma myofibril A band I band myofilament smooth endoplasmic reticulum (sarcoplasmic reticulum) terminal cisternae FIGURE 5-6 The myofibrils of skeletal muscle are comprised of myofilaments. Smooth endoplasmic reticulum surrounds each myofibril and forms terminal cisternae near the T tubule. T tubules extend into the cytoplasm from the cell membrane and surround the myofibrils at the A–I junction. A T tubule plus two terminal cisternae form a triad structure. Peripheral nuclei of the skeletal muscle myofiber are not shown in this illustration. Individual myocytes are bound together into primary bundles myosin-II binding sites on the actin. In addition, triple globular or fascicles (Fig. 5-7). Within a fascicle, an individual myocyte units of troponin are spaced at regular intervals along the tropo- is surrounded by reticular fibers, which form the endomysium. myosin. The globular subunits include TnT, which binds tro- Nerve fibers and an extensive network of continuous capillaries ponin to tropomyosin; TnC, which binds calcium; and TnI, which are also present in the endomysium. Each fascicle is surrounded binds to actin and prevents interaction with myosin. When calcium by dense irregular connective tissue, termed the perimysium. increases and binds to TnC, tropomyosin moves off the actin- Supplying blood vessels and nerves plus muscle stretch receptors binding site and allows myosin-II to interact with actin. (muscle spindles) are located in the perimysium. Most muscles Thick myofilaments are composed of myosin-II, formed are surrounded on the outer surface by a dense irregular connec- by two heavy chains and four light chains of amino acids. The tive tissue layer, the epimysium. The connective tissues of skeletal two heavy chains twist together to form a rodlike tail with two muscle are interconnected and provide a means by which contrac- protruding globular heads. Two light chains are associated with tile forces are transmitted to other tissues. each head. The heads have binding sites for actin and for adeno- sine triphosphate (ATP). In addition, they have adenosine tri- phosphatase (ATPase) activity. Individual thick filaments are Fine Structure bound by bands of C protein, which stabilize the filament. Contractile myofilaments of skeletal muscle cells are primarily The myofilaments are arranged to form the light and dark actin or myosin-II. In addition, the myofilaments contain other banding pattern visible in a longitudinal section of the myofibril proteins involved in either binding the primary filaments to- (Fig. 5-9). Adjacent thick myofilaments and overlapping thin gether (e.g., actinins, M-line proteins) or regulating the actin and myofilaments form the A band. Thin myofilaments do not ex- myosin-II interaction (e.g., tropomyosin, troponin). tend to the center of the A band, leaving a more lucent region Thin myofilaments of skeletal muscle are composed of actin, known as the H band. The thick myofilaments are intercon- troponin, and tropomyosin (Fig. 5-8). Globular molecules (G-actin) nected down the center of the H band by an M line. The M line within the myoblast polymerize to form filamentous strands contains myomesin, which links the M line to desmin, and cre- (F-actin). Each globular molecule has a binding site for myosin-II. atine phosphokinase, which helps maintain levels of ATP for Two filamentous strands twist together to form a double helix. contraction. The pseudo-H zone is present on either side of the Filamentous tropomyosin molecules lie in the groove between M line. In this region, thick myofilaments lack protruding cross- the two twisted strands of F-actin. The tropomyosin covers the bridges and the area appears more electron-lucent. 84 Dellmann’s Textbook of Veterinary Histology is associated with actin and may regulate the assembly and length of actin filaments. Desmin filaments, located at the Z line, link adjacent myofibrils together side by side, and also attach the myo- fibrils to the cell membrane at specializations called costameres. Dystrophin, a transmembrane complex of proteins, stabilizes the cell membrane of the myocyte and links the cell to the sur- rounding basement membrane. On the cytoplasmic side of the cell membrane, the dystrophin complex is linked to actin myo- filaments. The cell membrane (previously termed sarcolemma) invagi- nates at several sites to form a tubular network, the T tubules (Figs. 5-6 and 5-10). Within the cytoplasm of the myocyte, individual myofibrils are surrounded by highly specialized smooth endoplas- mic reticulum (sER) (sarcoplasmic reticulum), which stores cal- cium. The sER forms an anastomosing network of tubules around the myofibrils and dilates to create terminal cisternae at the A–I band junction. The membranes of the terminal cisternae have voltage-gated channels to release the stored calcium when needed. Each T tubule courses adjacent to two terminal cisternae and the three structures collectively form a triad. Mitochondria and glyco- gen granules are located in the cytoplasm between the myofibrils and provide energy during muscle contraction. Contraction A motor unit is composed of a nerve fiber (axon) and the muscle cells it innervates. One nerve fiber may innervate multiple myo- cytes. The axon contacts the skeletal muscle fiber and branches to form a motor end plate on the surface of the myocyte. When stimulated, an action potential travels down the axon and causes release of acetylcholine from the motor end plate into the synap- tic cleft adjacent to the muscle fiber. Acetylcholine binds to re- FIGURE 5-7 The myofibers are organized into fascicles (bundles) and separated from other fascicles by perimysium. Within ceptors on the cell membrane and opens receptor-gated sodium the larger divisions of the perimysium, notice the arteriole (A), channels into the myocyte. Sodium influxes into the muscle fiber venule (V), intramuscular nerve branch (N), and muscle spindle (*). and initiates a wave of depolarization that spreads across the cell At the margin of the section is a portion of the epimysium membrane. (arrowheads) (×125). In the resting state before depolarization of the cell membrane, the tropomyosin–troponin complex covers the myosin-II binding sites on the actin filament (Fig. 5-8). Myosin-II heads are bound to ATP. As depolarization begins, an action potential spreads across In a cross section of the myofibril within the A band, groups the cell membrane and extends into the T tubules. The depolar- of six thin myofilaments surround one thick myofilament to ization causes the adjacent terminal cisternae to release stored cal- form a hexagonal lattice. The thick myofilaments are linked to cium into the cytoplasm around the myofibrils. The calcium binds each other by myosin-II cross-bridges (side arms that protrude to troponin (TnC) on the thin myofilaments, causing the troponin from the filaments) in the A band, except in the pseudo-H zone, to undergo a conformation change. The change in troponin results where cross-bridges are absent. in the movement of tropomyosin to expose the myosin-II binding The I band is composed of the portion of the thin filaments sites. Actin and myosin-II interact, allowing the increased hydrol- that do not extend into the A band. These thin myofilaments are ysis of ATP. Energy from the ATP hydrolysis is used to bend the interconnected in the center of the I band by a Z line composed head of the myosin-II complex. The movement of the head pulls of -actinin. A sarcomere extends from one Z line to the next the attached actin toward the center of the sarcomere, thus short- and represents the repeating unit of myofilament arrangement ening the sarcomere and contracting the myocyte overall. The within the myofibril. myosin-II head binds to a new ATP and then detaches from the Several structural proteins that link the contractile myo- actin filament and the cycle repeats. If ATP is depleted, the fila- filaments are found within skeletal muscle. Springlike titin an- ments cannot detach and rigor mortis sets in. After depolarization chors the Z line to myosin-II filaments and the M line and helps ends, calcium is actively transported back into the terminal cister- maintain the A band width when muscle is stretched. Nebulin nae and contraction ceases.  Muscle Jo Ann Eurell 85 G-actin molecule troponin complex myosin II tropomyosin heavy chains myosin II A light chains B C D FIGURE 5-8 Schematic representation of a thin myofilament (actin, troponin, tropomyosin) and a myosin-II molecule. Several myosin-II molecules aggregate to form a thick myofilament. A. The muscle is relaxed; actin and myosin-II are not linked. B. As contraction begins, the troponin–tropomyosin complex moves off the actin-binding site and allows myosin-II to bind. The myosin-II head then bends. C. The thin myofilament is pulled toward the center of the sarcomere (to the left in this drawing). D. The actin–myosin complex then dissociates, troponin–tropomyosin covers the actin-binding site, and the myosin head swings forward to repeat the cycle. 86 Dellmann’s Textbook of Veterinary Histology dividual muscles, variable distribution of fiber types occurs. The fiber types are identified by using antibodies against either fast- or slow-twitch myosin isotypes. Fast muscle fibers contract quickly while slow muscle fibers contract more slowly. Red skeletal mus- cle fibers contain large amounts of myoglobin, which contributes to their red color. Myoglobin is an oxygen-carrying protein simi- lar to hemoglobin. The red fibers have extensive mitochondria, which are densely packed under the sarcolemma and between myo- fibrils. This type of skeletal muscle fiber depends on the oxidative pathway for energy production. Most red muscle fibers contract and fatigue slowly and are termed slow-twitch fibers; however, some fast-twitch red fibers do exist. In contrast to red muscle fibers, white muscle fibers have less myoglobin and are lighter in color. Fewer mitochondria are present, often clustering as pairs between C myofibrils near the I bands. The sER is more extensive, allowing for rapid release of calcium to initiate contraction. The energy for white muscle fiber contraction is primarily from anaerobic glyco- lysis. White muscle fibers contract and fatigue more rapidly com- pared with red muscle fibers and are known as fast-twitch fibers. Intermediate muscle fibers have characteristics of both red and white fibers. Myogenesis, Hypertrophy, Atrophy, and Regeneration During development, mesenchymal cells differentiate into skele- tal muscle myoblasts. Myoblasts may migrate to remote loca- tions from their original site of development. As development progresses, multiple myoblasts fuse and form elongated myo- tubes. Within the myotube, contractile myofibrils are formed. FIGURE 5-9 Light micrograph (A) and electron micrograph (B) of longitudinally oriented skeletal muscle and schematic As additional myoblasts fuse to the developing myocyte and myo- representation (C) of a sarcomere. In A, transverse striations fibrils increase in number, the nuclei peripheralize within the cell. consisting of alternating light bands (I bands) and dark bands (A Satellite cells remain as potential myogenic cells within the basal bands) are present. Each I band is bisected by a Z line (arrowheads) lamina next to the mature myocyte. (×1150). In B, the transverse striations can be further resolved into Hypertrophy of mature muscle cells occurs through the ac- Z lines (Z) that define a sarcomere and bisect the light I band (not tivity of satellite cells. One satellite cell divides into two daugh- labeled). The A band is electron-dense and is bisected by the M line ter cells. One daughter cell remains as a satellite cell, whereas the (M, arrowhead), which connects adjacent thick myofilaments. On other fuses with the muscle cell and adds additional nuclei. The either side of the M line, an electron-lucent area represents the H new nuclei direct the synthesis of additional myofibrils and other band (H), where there is no overlap of thick and thin myofilaments (×22,500). In C, the arrangement of myofilaments is shown in cytoplasmic elements. Neither the myocyte nor its nuclei divide relation to the electron micrograph. PH is the pseudo-H zone, a during the process of hypertrophy. In contrast, during atrophy of more electron-lucent region in which thick myofilaments lack skeletal muscle, myofibrils and nuclei are lost. cross-bridges. The bottom diagram represents a cross section of Regeneration of muscle is dependent on the extent of injury. the region indicated by the arrows. Large dots represent thick Small areas of muscle can be regenerated through fusion of satel- myofilaments and small dots represent thin myofilaments. lite cells with each other to form new muscle cells or fusion with existing muscle cells. If damage is extensive, muscle is replaced During contraction, the I and H bands narrow and the Z lines by connective tissue instead. move closer together. When muscle is stretched, opposite changes occur. In contrast, the width of the A band remains constant dur- ing either contraction or stretching. CARDIAC MUSCLE Classification of Skeletal Muscle Fibers Light Microscopic Structure Skeletal muscle fibers can be classified based on speed of contrac- The striated myocytes of cardiac muscle branch and anastomose tion, gross anatomic appearance, and fatigue resistance. Within in- (Fig. 5-11). At the end-to-end junction of adjacent cells, dense  Muscle Jo Ann Eurell 87 FIGURE 5-10 Electron micrograph of a longitudinal section through a skeletal muscle cell. Structures identified include: A band (A); I band (I); Z line (Z); M line (M); pseudo-H band (H); glycogen (G) within the cytoplasm adjacent to mitochondria; terminal cisternae (L); T tubule (T); and other triads (*) located at the A–I junction (×34,000). intercalated disks are present. Cardiac myocytes are approxi- mately 15 µm in diameter and 85 to 100 µm in length. The sin- gle nuclei of cardiac muscle cells are located in the center of the cell and the cytoplasm is acidophilic (Fig. 5-12). A network of fine reticular and collagenous fibers surrounds each cardiac muscle fiber. The network corresponds to endomy- sium of skeletal muscle but is more irregular. In the heart, cardiac myocytes are subdivided into groups by dense connective tissue analogous to the perimysium of skeletal muscle. No tissue that corresponds to skeletal muscle epimysium is present. Individual cardiac myocytes are surrounded by a well-developed capillary network (Figs. 5-11 and 5-12). Fine Structure Cardiac myocytes have myofibrils similar to skeletal muscle (Fig. 5-13). The same banding pattern of myofilaments is present. FIGURE 5-11 Cardiac myocytes in longitudinal section. Note T tubules, located at the Z line, are larger than in skeletal mus- the transverse striations and branching of the myocytes, the central cle (Fig. 5-14). The sarcoplasmic reticulum is usually present on location of their nuclei, and the dark-stained intercalated disks one side of the T tubule, forming a diad instead of a triad as found (arrows). This muscle type has many capillaries (C) (×700). in skeletal muscle. 88 Dellmann’s Textbook of Veterinary Histology The mitochondria of cardiac myocytes are larger and more numerous than in skeletal muscle, indicating the degree of aero- bic metabolism that occurs in this tissue (Fig. 5-14). The cyto- plasm also contains lipid droplets and glycogen. The intercalated disk is the means by which cardiac muscle cells are linked (Figs 5-13 and 5-15). The disk is formed by a complex interdigitation of the adjacent cell membranes. The lon- gitudinal region of the disk contains gap junctions, which allow transfer of chemical signals between adjacent cells. Desmosomes and fasciae adherens are present in the transverse region of the disk. The desmosomes have intermediate filaments that extend into the cytoplasm and result in strong attachment between cells. Actin filaments of the myofibrils anchor into a specialized region of the myocyte membrane, the fascia adherens, located between the desmosomes (Fig. 5-15). Atrial myocytes are smaller and have fewer T tubules than FIGURE 5-12 Cardiac muscle, cross section. Note the centrally myocytes of the ventricle. In addition, atrial cardiac muscle has located nuclei (arrow) and numerous capillaries (C). Hematoxylin membrane-bounded dense granules in the cytoplasm that con- and eosin (×800). tain atrial natriuretic peptides (ANPs). ANPs stimulate the inner medullary collecting ducts of the kidney to excrete sodium reticular fibers smooth T tubule Z line intercalated endoplasmic disk reticulum (sarcoplasmic reticulum) FIGURE 5-13 The T tubules of cardiac muscle are located at the Z line. Smooth endoplasmic reticulum surrounds the myofibrils and contacts the T tubules, forming a diad structure. The ends of the adjacent muscle fibers are joined by an intercalated disk. A nucleus, which is centrally located in the cardiac muscle fiber, is not shown in this drawing.  Muscle Jo Ann Eurell 89 FIGURE 5-14 Electron micrograph of a longitudinal section of cardiac muscle. The cell membrane and basement membrane of each myocyte are indicated with arrowheads. Large mitochondria (M) with densely packed cristae are located just below the cell membrane. Note the two large T tubules (T) entering the lower myocyte at the Z lines. Diads (D) composed of a T tubule and smooth endoplasmic reticulum are present deeper in the cell between the myofibrils (×22,500). (Courtesy of W. S. Tyler.) (natriuresis) and water (diuresis). The peptides also cause vascu- Contraction lar smooth muscle to relax. Cardiac muscle is stimulated to contract by a mechanism similar to skeletal muscle. As there is less sER in cardiac muscle, an ac- Cardiac Nodes and Impulse tion potential triggers the release of calcium from both the sER Conduction Fibers and T tubules. Contraction is activated through the interaction of actin and myosin myofilaments. Sequential contraction of Modified cardiac muscle cells form the cardiac nodes and im- heart chambers is stimulated by the orderly spread of the action pulse conduction fibers (Purkinje fibers) (Fig. 5-16 and Chap- potentials via gap junctions in the intercalated disks. The num- ter 7). The cells of the sinoatrial and atrioventricular nodes are ber, size, and distribution of the gap junctions plus the type of clustered together and have more cytoplasm and fewer myofibrils connexin (the structural protein of the gap junctions) influence than cardiac myocytes, accounting for their light-staining cyto- the rate of impulse conduction. plasm. A large, pale area near the nucleus represents the storage site of glycogen, which is removed during tissue processing. The cells stain positively for acetylcholinesterase, which relates to their Myogenesis, Hypertrophy, conductive function. At the ultrastructural level, the cells have and Regeneration mitochondria and sarcoplasmic reticulum but lack T tubules. The atrioventricular bundle, composed of impulse conduction fibers Cardiac muscle develops from splanchnic mesoderm surround- similar to nodal cells, originates from the atrioventricular node ing the endocardial heart tube. The fibers arise by differentiation and supplies both ventricles. As the fibers course toward the apex and growth of single cells. As the cells grow, new myofilaments of the heart, they become larger than adjacent cardiac myocytes form. The ability of cardiac muscle cells to divide is lost soon after and are a prominent feature of the subendocardium. birth. Enlargement of the heart wall during exercise or cardiac 90 Dellmann’s Textbook of Veterinary Histology FIGURE 5-15 Electron micrograph of an intercalated disk from cardiac muscle. The fascia adherens junction (*) is oriented transversely to the long axis of the myofibril. Desmosomes are indicated by the double arrow. Gap junctions (arrowheads) are oriented parallel to the long axis (×42,100). (Courtesy of W. S. Tyler.) insufficiencies is primarily through hypertrophy rather than FIGURE 5-16 Cardiac impulse conduction fibers (one is hyperplasia. Damage to a section of the heart wall, with the outlined by arrows) are larger than myocytes. They have a centrally resulting death of that section, is repaired primarily by prolifer- located nucleus and sparse myofibrils (mf) in their cytoplasm. ation of connective tissue rather than by regeneration of any sig- PTAH stain (×1200). nificant number of new cardiac myocytes. Stem cells are under investigation as a possible source of replacement cells for dam- aged cardiac muscle cells. Huxley HE. Electron microscopy studies of the structure of natural and synthetic protein filaments from striated muscle. J Mol Biol 1963; 7:281–308. SUGGESTED READINGS Huxley HE. The structural basis of contraction and regulation in skeletal muscle. In: Heilmeyer LMG, Rüegg JC, Wieland T, eds. Alberts B, Bray D, Lewis J, et al. Molecular Biology of the Cell. 3rd Ed. Molecular Basis of Motility. New York: Springer-Verlag, 1976. New York: Garland Publishing, 1994. Jones DA, Round JM. Skeletal Muscle in Health and Disease. New Allt G, Lawrenson JG. Pericytes: cell biology and pathology. Cell Tiss York: Manchester University Press, 1990. Org 2001;169:1–11. Pardo JV, Siliciano JD, Craig SW. A vinculin-containing cortical lat- Cardinet GH III, Leong DL, Means PS. Myocyte differentiation in nor- tice in skeletal muscle: transverse lattice elements (“costameres”) mal and hypotrophied canine pectineal muscles. Muscle Nerve mark sites of attachment between myofibrils and sarcolemma. Proc 1982;5:665. Natl Acad Sci U S A 1983;80:1008–1012. Cardinet GH III, Orvis JA. Skeletal muscle function. In: Kaneko J, ed. Peachey LD, ed. Handbook of Physiology. Section 10: Skeletal Muscle. Clinical Biochemistry of Domestic Animals. New York: Academic Bethesda, MD: American Physiological Society, 1983. Press, 1980. Pollard TD, Earnshaw WC. Cell Biology. Philadelphia: Saunders, 2002. Dellmann HD, Carithers JR. Cytology and Microscopic Anatomy. Severs NJ. Cardiac muscle cell interaction: from microanatomy to the Baltimore: Williams & Wilkins, 1996. molecular make-up of the gap junction. Histol Histopathol 1995; Ebashi S. Excitation-contraction coupling. Ann Rev Physiol 1976;36: 10:481–501. 293–313. Tokuyasu KT, Dutton AH, Singer SJ. Immunoelectron microscopic Guyton AC, Hall JE. Textbook of Medical Physiology. Philadelphia: studies of desmin (skeleton) localization and intermediate fila- WB Saunders, 1996. ment organization in chicken cardiac muscle. J Cell Biol 1983;96: Hill M, Wernig A, Goldspink, G. Muscle satellite (stem) cell activation 1736–1742. during local tissue injury and repair. J Anat 2003:203:89–99. Wang K, Ramirez-Mitchell R. A network of transverse and longitudi- Horowitz A, Menice CB, Laporte R, et al. Mechanisms of smooth muscle nal intermediate filaments is associated with sarcomeres of adult contraction. Physiol Rev 1996;76:967–1003. vertebrate skeletal muscle. J Cell Biol 1983;96:562–570.