Junqueira's Basic Histology, Text and Atlas, 14th Edition PDF

C H A P T E R SKELETAL MUSCLE 10 Muscle Tissue 193 CARDIAC MUSCLE 207 Organization of a Skeletal Muscle...

C H A P T E R SKELETAL MUSCLE 10 Muscle Tissue 193 CARDIAC MUSCLE 207 Organization of a Skeletal Muscle 194 SMOOTH MUSCLE 208 Organization Within Muscle Fibers 194 REGENERATION OF MUSCLE TISSUE 213 Sarcoplasmic Reticulum & Transverse Tubule System 197 SUMMARY OF KEY POINTS 213 Mechanism of Contraction 198 ASSESS YOUR KNOWLEDGE 214 Innervation 200 Muscle Spindles & Tendon Organs 203 Skeletal Muscle Fiber Types 205 M uscle tissue, the fourth basic tissue type with epi- thing formed), the smooth ER is the sarcoplasmic reticu- thelia, connective tissues, and nervous tissue, is lum, and the muscle cell membrane and its external lamina composed of cells that optimize the universal cell are the sarcolemma (sarkos + Gr. lemma, husk). property of contractility. As in all cells, actin microfilaments and associated proteins generate the forces necessary for the muscle contraction, which drives movement within organ › › MEDICAL APPLICATION systems, of blood, and of the body as a whole. Essentially all The variation in diameter of muscle fibers depends on muscle cells are of mesodermal origin and differentiate by a factors such as the specific muscle, age, gender, nutritional gradual process of cell lengthening with abundant synthesis of status, and physical training of the individual. Exercise the myofibrillar proteins actin and myosin. enlarges the skeletal musculature by stimulating formation Three types of muscle tissue can be distinguished on the basis of new myofibrils and growth in the diameter of individual of morphologic and functional characteristics (Figure 10–1), muscle fibers. This process, characterized by increased cell with the structure of each adapted to its physiologic role. volume, is called hypertrophy (Gr. hyper, above + trophe, Skeletal muscle contains bundles of very long, multi- nourishment). Tissue growth by an increase in the number nucleated cells with cross-striations. Their contraction is of cells is termed hyperplasia (hyper + Gr. plasis, molding), quick, forceful, and usually under voluntary control. which takes place very readily in smooth muscle, whose Cardiac muscle also has cross-striations and is com- cells have not lost the capacity to divide by mitosis. posed of elongated, o%en branched cells bound to one another at structures called intercalated discs that are › SKELETAL MUSCLE unique to cardiac muscle. Contraction is involuntary, vigorous, and rhythmic. Smooth muscle consists of collections of fusiform Skeletal (or striated) muscle consists of muscle fibers, cells that lack striations and have slow, involuntary which are long, cylindrical multinucleated cells with diam- contractions. eters of 10-100 μm. During embryonic muscle development, In all types of muscle, contraction is caused by the slid- mesenchymal myoblasts (L. myo, muscle) fuse, forming myo- ing interaction of thick myosin filaments along thin actin fila- tubes with many nuclei. Myotubes then further differentiate to ments. The forces necessary for sliding are generated by other form striated muscle fibers (Figure 10–2). Elongated nuclei are proteins affecting the weak interactions in the bridges between found peripherally just under the sarcolemma, a characteristic actin and myosin. nuclear location unique to skeletal muscle fibers/cells. A small As with neurons, muscle specialists refer to certain mus- population of reserve progenitor cells called muscle satellite cle cell organelles with special names. The cytoplasm of mus- cells remains adjacent to most fibers of differentiated skeletal cle cells is o%en called sarcoplasm (Gr. sarkos, flesh + plasma, muscle. 193 194 CHAPTER 10 Muscle Tissue FIGURE 10–1 Three types of muscle. Striations Connective Intercalated disc Glycogen Nuclei Muscle fiber tissue Branching Striations Nucleus Nuclei Muscle cells (a) Skeletal muscle (b) Cardiac muscle (c) Smooth muscle Light micrographs of each type, accompanied by labeled drawings. involuntary contractions. (c) Smooth muscle is composed of (a) Skeletal muscle is composed of large, elongated, multinucle- grouped, fusiform cells with weak, involuntary contractions. The ated fibers that show strong, quick, voluntary contractions. (b) density of intercellular packing seen reflects the small amount of Cardiac muscle is composed of irregular branched cells bound extracellular connective tissue present. ([a, b]: X200; [c]: X300; together longitudinally by intercalated discs and shows strong, All H&E) Organization of a Skeletal Muscle Collagens in these connective tissue layers of muscle serve to transmit the mechanical forces generated by the contract- Thin layers of connective tissue surround and organize the ing muscle cells/fibers; individual muscle fibers seldom extend contractile fibers in all three types of muscle, and these layers from one end of a muscle to the other. are seen particularly well in skeletal muscle (Figures 10–3 and All three layers, plus the dense irregular connective tissue 10–4). The concentric organization given by these supportive of the deep fascia which overlies the epimysium, are continu- layers resembles that in large peripheral nerves: ous with the tough connective tissue of a tendon at myoten- The epimysium, an external sheath of dense irregular dinous junctions which join the muscle to bone, skin, or connective tissue, surrounds the entire muscle. Septa another muscle (Figures 10–3 and 10–4c). Ultrastructural of this tissue extend inward, carrying the larger nerves, studies show that in these transitional regions, collagen fibers blood vessels, and lymphatics of the muscle. from the tendon insert themselves among muscle fibers and The perimysium is a thin connective tissue layer that associate directly with complex infoldings of sarcolemma. immediately surrounds each bundle of muscle fibers termed a fascicle (Figure 10–3). Each fascicle of muscle fibers makes up a functional unit in which the fibers Organization Within Muscle Fibers work together. Nerves, blood vessels, and lymphatics Longitudinally sectioned skeletal muscle fibers show striations penetrate the perimysium to supply each fascicle. of alternating light and dark bands (Figure 10–6a). The sarco- Within fascicles a very thin, delicate layer of reticular plasm is highly organized, containing primarily long cylindrical fibers and scattered fibroblasts, the endomysium, sur- filament bundles called myofibrils that run parallel to the long rounds the external lamina of individual muscle fibers. axis of the fiber (Figure 10–6b). The dark bands on the myofi- In addition to nerve fibers, capillaries form a rich net- brils are called A bands (anisotropic or birefringent in polarized work in the endomysium bringing O2 to the muscle light microscopy); the light bands are called I bands (isotropic, fibers (Figure 10–5). do not alter polarized light). In the TEM (Figure 10–6c), each I  Skeletal Muscle 195 FIGURE 10–2 Development of skeletal muscle. FIGURE 10–3 Organization of skeletal muscle. C H A P T E R Myoblasts Satellite cell Myoblast Tendon 1 0 fusion to form myotubes Muscle Tissue Skeletal Muscle Deep fascia Epimysium Skeletal muscle Differentiation Satellite cell Muscle fiber Artery Skeletal muscle begins to differentiate when mesenchymal Vein Perimysium cells, called myoblasts, align and fuse together to make longer, Nerve multinucleated tubes called myotubes. Myotubes synthesize Fascicle the proteins to make up myofilaments and gradually begin to show cross-striations by light microscopy. Myotubes continue differentiating to form functional myofilaments, and the nuclei are displaced against the sarcolemma. Part of the myoblast population does not fuse and differenti- ate but remains as a group of mesenchymal cells called muscle Endomysium satellite cells located on the external surface of muscle fibers inside the developing external lamina. Satellite cells proliferate and produce new muscle fibers following muscle injury. Muscle fiber band is seen to be bisected by a dark transverse line, the Z disc (Ger. zwischen, between). The repetitive functional subunit of the contractile apparatus, the sarcomere, extends from Z disc to Z disc (Figure 10–6c) and is about 2.5-μm long in resting muscle. Mitochondria and sarcoplasmic reticulum are found between the myofibrils, which typically have diameters of 1-2 μm. Myofibrils consist of an end-to-end repetitive arrange- An entire skeletal muscle is enclosed within a thick layer of ment of sarcomeres (Figure 10–7); the lateral registration of dense connective tissue called the epimysium that is con- sarcomeres in adjacent myofibrils causes the entire muscle tinuous with fascia and the tendon binding muscle to bone. fiber to exhibit a characteristic pattern of transverse striations. Large muscles contain several fascicles of muscle tissue, each The A and I banding pattern in sarcomeres is due mainly wrapped in a thin but dense connective tissue layer called the to the regular arrangement of thick and thin myofilaments, perimysium. Within fascicles individual muscle fibers (elon- gated multinuclear cells) are surrounded by a delicate connec- composed of myosin and F-actin, respectively, organized tive tissue layer, the endomysium. within each myofibril in a symmetric pattern containing thou- sands of each filament type (Figure 10–7). The thick myosin filaments are 1.6-μm long and 15-nm wide; they occupy the A band at the middle region of the sar- thick and thin filaments, and ATP, catalyzing energy release comere. Myosin is a large complex (∼500 kDa) with two iden- (actomyosin ATPase activity). Several hundred myosin tical heavy chains and two pairs of light chains. Myosin heavy molecules are arranged within each thick filament with over- chains are thin, rodlike motor proteins (150-nm long and lapping rodlike portions and the globular heads directed 2-3 nm thick) twisted together as myosin tails (Figure 10–7). toward either end (Figure 10–7a). Globular projections containing the four myosin light chains The thin, helical actin filaments are each 1.0-μm long and form a head at one end of each heavy chain. The myosin heads 8-nm wide and run between the thick filaments. Each G-actin bind both actin, forming transient crossbridges between the monomer contains a binding site for myosin (Figure 10–7b). 196 CHAPTER 10 Muscle Tissue P FIGURE 10–4 Skeletal muscle. P a a P En E P a b b M T M T M M M C M C b (a) A cross section of striated muscle demonstrating all three layers of the muscle fibers, surrounded by endomysium. of connective tissue and cell nuclei. The endomysium (En) sur- (X400; Immunoperoxidase) rounds individual muscle, and perimysium (P) encloses a group (c) Longitudinal section of a myotendinous junction. Tendons of muscle M T(E) sur- fibers comprising a fascicle. A thick epimysium develop together with skeletal muscles and join muscles to the rounds the entire muscle. All three of these tissues contain colla- periosteum of bones. The dense collagen fibers of a tendon (T) are gen types I and III (reticulin). (X200; H&E) continuous with those in the three connective tissue layers around (b) An adjacent section immunohistochemically stained for muscle fibers (M), forming a strong unit that allows muscle con- laminin, which specifically stains the external laminae traction to move other structures. (X400; H&E) M FIGURE 10–5 Capillaries of skeletalMmuscle. C The blood vessels were injected with a dark plastic polymer before the muscle was collected and sectioned longitudinally. A rich network of capillaries in endomysium surrounding muscle fibers is revealed by this method. (X200; Giemsa with polarized light)  Skeletal Muscle 197 The thin filaments have two tightly associated regulatory pro- FIGURE 10–6 Striated skeletal muscle in teins (Figure 10–7b): C H A P T E R longitudinal section. Tropomyosin, a 40-nm-long coil of two polypeptide chains located in the groove between the two twisted A actin strands I Troponin, a complex of three subunits: TnT, which attaches to tropomyosin; TnC, which binds Ca2+; and TnI, which regulates the actin-myosin interaction 1 0 F Troponin complexes attach at specific sites regularly spaced along each tropomyosin molecule. Muscle Tissue Skeletal Muscle The organization of important myofibril components is a shown in Figure 10–8. I bands consist of the portions of the N thin filaments that do not overlap the thick filaments in the A bands, which is why I bands stain more lightly than A bands. Actin filaments are anchored perpendicularly on the Z disc by the actin-binding protein α-actinin and exhibit opposite polarity on each side of this disc (Figure 10–8c). An important accessory protein in I bands is titin (3700 kDa), the largest protein in the body, with scaffolding and elastic properties, which supports the thick myofilaments and connects them to the Z disc (Figure 10–8c). Another large accessory protein, nebulin, binds each thin myofilament laterally, helps anchor them to (-actinin, and specifies the length of the actin poly- mers during myogenesis. b The A bands contain both the thick filaments and the overlapping portions of thin filaments. Close observation of I the A band shows the presence of a lighter zone in its cen- ter, the H zone, corresponding to a region with only the rod- Z A Z like portions of the myosin molecule and no thin filaments (Figure 10–8c). Bisecting the H zone is the M line (Ger. Mitte, middle; Figure 10–8d), containing a myosin-binding protein M M myomesin that holds the thick filaments in place, and cre- atine kinase. This enzyme catalyzes transfer of phosphate H groups from phosphocreatine, a storage form of high-energy c phosphate groups, to ADP, helping to supply ATP for muscle contraction. Despite the many proteins present in sarcomeres, myo- Longitudinal sections reveal the striations characteristic of skeletal sin and actin together represent over half of the total protein muscle. in striated muscle. The overlapping arrangement of thin and (a) Parts of three muscle fibers are separated by very thin endo- mysium that includes one fibroblast nucleus (F). Muscle nuclei (N) thick filaments within sarcomeres produces in TEM cross sec- are found against the sarcolemma. Along each fiber thousands of tions hexagonal patterns of structures that were important in dark-staining A bands alternate with lighter I bands. (X200; H&E) determining the functions of the filaments and other proteins (b) At higher magnification, each fiber can be seen to have three or in the myofibril (Figures 10–8b and 10–8e). four myofibrils, here with their striations slightly out of alignment with one another. Myofibrils are cylindrical bundles of thick and thin myofilaments that fill most of each muscle fiber. (X500; Giemsa) Sarcoplasmic Reticulum & Transverse Tubule (c) TEM showing one contractile unit (sarcomere) in the long System series that comprises a myofibril. In its middle is an electron- In skeletal muscle fibers the membranous smooth ER, called dense A band bisected by a narrow, less dense region called the H zone. On each side of the A band are the lighter-stained I here sarcoplasmic reticulum, contains pumps and other bands, each bisected by a dense Z disc which marks one end of proteins for Ca2+ sequestration and surrounds the myofibrils the sarcomere. Mitochondria (M), glycogen granules, and small (Figure 10–9). Calcium release from cisternae of the sarcoplas- cisternae of SER occur around the Z disc. (X24,000) mic reticulum through voltage-gated Ca2+ channels is triggered (Figure 10–6c, used with permission from Mikel H. Snow, by membrane depolarization produced by a motor nerve. Department of Cell and Neurobiology, Keck School of Medicine at To trigger Ca 2+ release from sarcoplasmic reticulum the University of Southern California, Los Angeles.) throughout the muscle fiber simultaneously and produce 198 CHAPTER 10 Muscle Tissue FIGURE 10–7 Molecules composing thin and thick filaments. Muscle fiber Myofibril Myofilaments Myosin molecule Heads Tail Actin-binding site ATP- and ATPase-binding site Myosin heads a Thick filament Tropomyosin Troponin Ca2+-binding site G-actin F-actin Myosin-binding site b Thin filament Myofilaments, which include both thick and thin filaments, consist myofilament contains 200-500 molecules of myosin. (b) A thin of contractile protein arrays bundled within myofibrils. (a) A thick filament contains F-actin, tropomyosin, and troponin. uniform contraction of all myofibrils, the sarcolemma overlapping thin and thick filaments of each sarcomere slide has tubular infoldings called transverse or T-tubules past one another. (Figures 10–9 and 10–10). These long fingerlike invagi- Contraction is induced when an action potential arrives nations of the cell membrane penetrate deeply into the at a synapse, the neuromuscular junction (NMJ), and is sarcoplasm and encircle each myofibril near the aligned transmitted along the T-tubules to terminal cisternae of the A- and I-band boundaries of sarcomeres. sarcoplasmic reticulum to trigger Ca2+ release. In a resting Adjacent to each T-tubule are expanded terminal cister- muscle, the myosin heads cannot bind actin because the bind- nae of sarcoplasmic reticulum. In longitudinal TEM sections, ing sites are blocked by the troponin-tropomyosin complex this complex of a T-tubule with two terminal cisternae is called on the F-actin filaments. Calcium ions released upon neural a triad (Figures 10–9 and 10–10). The triad complex allows stimulation bind troponin, changing its shape and moving depolarization of the sarcolemma in a T-tubule to affect the tropomyosin on the F-actin to expose the myosin-binding sarcoplasmic reticulum and trigger release of Ca2+ ions into active sites and allow crossbridges to form. Binding actin pro- cytoplasm around the thick and thin filaments, which initiates duces a conformational change or pivot in the myosins, which contraction of sarcomeres. pulls the thin filaments farther into the A band, toward the Z disc (Figure 10–11). Energy for the myosin head pivot which pulls actin is pro- Mechanism of Contraction vided by hydrolysis of ATP bound to the myosin heads, a%er Figure 10–11 summarizes the key molecular events of mus- which myosin binds another ATP and detaches from actin. In cle contraction. During this process neither the thick nor the continued presence of Ca2+ and ATP, these attach-pivot- thin filaments change their length. Contraction occurs as the detach events occur in a repeating cycle, each lasting about FIGURE 10–8 Structure of a myofibril: A series of sarcomeres. C H A P T E R Connectin Titin Thin Thick Thick Thin filaments filament filament filament filament filament 1 0 Muscle Tissue Skeletal Muscle I band Z disc I band M line H zone A band b A band Myofibrils Z disc M line Z disc H zone Sarcomere a A Sarcomere Thin filament M line H zone I Thick filament e Z disc Titin Z disc I band A band I band c Sarcomere M line Z disc Z disc H zone d I band A band I band (a) The diagram shows that each muscle fiber contains several par- (d) The molecular organization of the sarcomeres produces stain- allel bundles called myofibrils. ing differences that cause the dark- and light-staining bands seen (b) Each myofibril consists of a long series of sarcomeres, separated by light microscopy and TEM. (X28,000) by Z discs and containing thick and thin filaments that overlap in (e) With the TEM an oblique section of myofibrils includes both certain regions. A and I bands and shows hexagonal patterns that indicate the (c) Thin filaments are actin filaments with one end bound to relationships between thin and thick myofilaments and other pro- α-actinin in the Z disc. Thick filaments are bundles of myosin, teins, as shown in part b of this figure. Thin and thick filaments are which span the entire A band and are bound to proteins of the arranged so that each myosin bundle contacts six actin filaments. M line and to the Z disc across the I bands by a very large protein Large mitochondria in cross section and SER cisternae are seen called titin, which has springlike domains. between the myofibrils. (X45,000) 200 CHAPTER 10 Muscle Tissue FIGURE 10–9 Organization of a skeletal muscle fiber Triad T-tubule Terminal cisterna Sarcoplasmic Muscle reticulum Fascicle Sarcoplasmic Triad Muscle fiber reticulum (SR) T-tubule Terminal cisternae of SR Sarcolemma Nucleus Myofibrils Sarcomere Thin & thick Myofilaments Nucleus Openings into T-tubules Sarcoplasm Nucleus Mitochondrion Skeletal muscle fibers are composed mainly of myofibrils. Each terminal cisternae of the sarcoplasmic reticulum. A T-tubule and its myofibril extends the length of the fiber and is surrounded by parts two associated terminal cisterna comprise a “triad” of small spaces of the sarcoplasmic reticulum. The sarcolemma has deep invagina- along the surface of the myofibrils. tions called T-tubules, each of which becomes associated with two 50 milliseconds, which rapidly shorten the sarcomere and branches and cover their points of contact with the muscle contract the muscle (Figures 10–11 and 10–12). A single mus- cells (Figure 10–13); the external lamina of the Schwann cell cle contraction results from hundreds of these cycles. fuses with that of the sarcolemma. Each axonal branch forms a When the neural impulse stops and levels of free Ca2+ dilated termination situated within a trough on the muscle cell ions diminish, tropomyosin again covers the myosin-binding surface, which are part of the synapses termed the neuromus- sites on actin and the filaments passively slide back and sar- cular junctions, or motor end plates (MEP) (Figure 10–13). comeres return to their relaxed length (Figure 10–11). In As in all synapses the axon terminal contains mitochondria the absence of ATP, the actin-myosin crossbridges become and numerous synaptic vesicles; here the vesicles contain the stable, which accounts for the rigidity of skeletal muscles neurotransmitter acetylcholine. Between the axon and the (rigor mortis) that occurs as mitochondrial activity stops muscle is the synaptic cleft. Adjacent to the synaptic cle%, the a%er death. sarcolemma is thrown into numerous deep junctional folds, which provide for greater postsynaptic surface area and more transmembrane acetylcholine receptors. Innervation When a nerve action potential reaches the MEP, acetyl- Myelinated motor nerves branch out within the perimysium, choline is liberated from the axon terminal, diffuses across the where each nerve gives rise to several unmyelinated terminal cle%, and binds to its receptors in the folded sarcolemma. The twigs that pass through endomysium and form synapses with acetylcholine receptor contains a nonselective cation chan- individual muscle fibers. Schwann cells enclose the small axon nel that opens upon neurotransmitter binding, allowing influx  Skeletal Muscle 201 FIGURE 10–10 Transverse tubule system and triads. C H A P T E R Tr G Tr T M 1 0 TC T TC I Z I A Muscle Tissue Skeletal Muscle A E T Tr G Tr M a b Transverse tubules are invaginations of the sarcolemma that pen- transverse tubule (T) and two adjacent terminal cisterns (TC) etrate deeply into the muscle fiber around all myofibrils. extending from the sarcoplasmic reticulum. Centrally located is the (a) TEM cross section of fish muscle shows portions of two fibers Z disc. Besides elements of the triad, sarcoplasm surrounding the and the endomysium (E) between them. Several transverse or myofibril also contains dense glycogen granules (G). T-tubules (T) are shown, perpendicular to the fiber surface, pen- Components of the triad are responsible for the cyclic release of etrating between myofibrils (M). (X50,000) Ca2+ from the cisternae and its sequestration again that occurs dur- ing muscle contraction and relaxation. The association between SR (b) Higher-magnification TEM of skeletal muscle in longitudinal cisternae and T-tubules is shown diagrammatically in Figure 10–11. section shows four membranous triads (Tr) cut transversely near (X90,000) the A-band–I-band junctions. Each triad consists of a central of cations, depolarizing the sarcolemma, and producing the muscles composed of many motor units, the firing of a single muscle action potential. Acetylcholine quickly dissociates motor axon will generate tension proportional to the number from its receptors, and free neurotransmitter is removed from of muscle fibers it innervates. Thus, the number of motor units the synaptic cle% by the extracellular enzyme acetylcholines- and their variable size control the intensity and precision of a terase, preventing prolonged contact of the transmitter with muscle contraction. its receptors. Key features of skeletal muscle cells, connective tissue, As discussed with Figure 10–11, the muscle action poten- contraction, and innervation are summarized in Table 10–1. tial moves along the sarcolemma and along T-tubules that penetrate deeply into sarcoplasm. At triads the depolarization signal triggers the release of Ca2+ from terminal cisterns of the › › MEDICAL APPLICATION sarcoplasmic reticulum, initiating the contraction cycle. Myasthenia gravis is an autoimmune disorder that involves An axon from a single motor neuron can form MEPs with circulating antibodies against proteins of acetylcholine one or many muscle fibers. Innervation of single muscle fibers receptors. Antibody binding to the antigenic sites interferes by single motor neurons provides precise control of muscle with acetylcholine activation of their receptors, leading to activity and occurs, for example, in the extraocular muscles intermittent periods of skeletal muscle weakness. As the for eye movements. Larger muscles with coarser movements body attempts to correct the condition, junctional folds have motor axons that typically branch profusely and inner- of sarcolemma with affected receptors are internalized, vate 100 or more muscle fibers. In this case the single axon digested by lysosomes, and replaced by newly formed recep- and all the muscle fibers in contact with its branches make up tors. These receptors, however, are again made unresponsive a motor unit. Individual striated muscle fibers do not show to acetylcholine by similar antibodies, and the disease follows graded contraction—they contract either all the way or not at a progressive course. The extraocular muscles of the eyes are all. To vary the force of contraction, the fibers within a mus- commonly the first affected. cle fascicle do not all contract at the same time. With large 202 CHAPTER 10 Muscle Tissue FIGURE 10–11 Events of muscle contraction. Synaptic knob 1 A nerve impulse triggers release of ACh from the synaptic knob into Sarcolemma the synaptic cleft. ACh binds to Synaptic vesicles ACh receptors in the motor end plate of the neuromuscular Neuromuscular Synaptic cleft Myofibril junction, initiating a muscle junction 1 impulse in the sarcolemma of the Muscle muscle fiber. impulse ACh Motor end ACh receptor plate 2 As the muscle impulse spreads quickly from the sarcolemma 2 along T tubules, calcium ions are Sarcoplasmic reticulum released from terminal cisternae into the sarcoplasm. Terminal cisternae T-tubule Calcium Actin Active site Troponin Tropomyosin Calcium Active sites blocked Crossbridge 5 When the impulse stops, calcium ions are actively 3 Calcium ions bind to troponin. Troponin changes shape, moving transported into the sarcoplasmic reticulum, tropomyosin on the actin to expose active sites on actin molecules tropomyosin re-covers active sites, and filaments of thin filaments. Myosin heads of thick filaments attach to exposed passively slide back to their relaxed state. active sites to form crossbridges. Active site Calcium Thin filament ATP ADP + P Thick filament 4 Myosin heads pivot, moving thin filaments toward the sarcomere center. ATP binds myosin heads and is broken down into ADP and P. Myosin heads detach from thin filaments and return to their prepivot position. The repeating cycle of attach-pivot-detach-return slides thick and thin filaments past one another. The sarcomere shortens and the muscle contracts. The cycle continues as long as calcium ions remain bound to troponin to keep active sites exposed.  Skeletal Muscle 203 FIGURE 10–12 Sliding filaments and sarcomere shortening in contraction. C H A P T E R Relaxed sarcomere Relaxed sarcomere Z disc Thick filament Z disc Titin Thin filament Thin filament M line Z disc Z disc M line 1 0 Muscle Tissue Skeletal Muscle H zone H zone I band A band I band I band A band I band a Relaxed skeletal muscle Contraction Contraction M line Z disc Z disc Z disc Z disc M line A band A band Fully contracted Fully contracted sarcomere sarcomere b Fully contracted skeletal muscle Diagrams and TEM micrographs show sarcomere shortening during muscle contraction, the Z discs at the sarcomere boundaries are skeletal muscle contraction. (a) In the relaxed state the sarcomere, drawn closer together as they move toward the ends of thick I band, and H zone are at their expanded length. The springlike filaments in the A band. Titin molecules are compressed during action of titin molecules, which span the I band, helps pull thin contraction. and thick filaments past one another in relaxed muscle. (b) During Muscle Spindles & Tendon Organs sensory nerves relay this information to the spinal cord. Dif- Striated muscles and myotendinous junctions contain sen- ferent types of sensory and intrafusal fibers mediate reflexes sory receptors acting as proprioceptors (L. proprius, one’s of varying complexity to help maintain posture and to regu- own + capio, to take), providing the central nervous system late the activity of opposing muscle groups involved in motor (CNS) with data from the musculoskeletal system. Among activities such as walking. the muscle fascicles are stretch detectors known as mus- A similar role is played by Golgi tendon organs, cle spindles, approximately 2-mm long and 0.1-mm wide much smaller encapsulated structures that enclose sensory (Figure 10–14a). A muscle spindle is encapsulated by modified axons penetrating among the collagen bundles at the myo- perimysium, with concentric layers of flattened cells, contain- tendinous junction (Figure 10–14a). Tendon organs detect ing interstitial fluid and a few thin muscle fibers filled with changes in tension within tendons produced by muscle con- nuclei and called intrafusal fibers (Figure 10–14). Several traction and act to inhibit motor nerve activity if tension sensory nerve axons penetrate each muscle spindle and wrap becomes excessive. Because both of these proprioceptors around individual intrafusal fibers. Changes in length (disten- detect increases in tension, they help regulate the amount of sion) of the surrounding (extrafusal) muscle fibers caused by effort required to perform movements that call for variable body movements are detected by the muscle spindles and the amounts of muscular force. 204 CHAPTER 10 Muscle Tissue FIGURE 10–13 The neuromuscular junction (NMJ). NB MEP MEP S MEP a Motor nerve fiber Myelin Axon terminal Schwann cell Synaptic vesicles (containing ACh) Active zone Sarcolemma Synaptic cleft Junctional Nucleus of muscle fiber Region of folds sarcolemma with ACh receptors b c Before it terminates in a skeletal muscle, each motor axon bundled terminally as an MEP embedded in a groove in the external lamina in the nerve forms many branches, each of which forms a synapse of the muscle fiber. with a muscle fiber. (c) Diagram of enclosed portion of the SEM indicating key features (a) Silver staining can reveal the nerve bundle (NB), the terminal of a typical MEP: synaptic vesicles of acetylcholine (ACh), a synaptic axonal twigs, and the motor end plates (MEP, also called neuro- cleft, and a postsynaptic membrane. This membrane, the sarco- muscular junctions or NMJ) on striated muscle fibers (S). (X1200) lemma, is highly folded to increase the number of ACh receptors (b) An SEM shows the branching ends of a motor axon, each at the MEP. Receptor binding initiates muscle fiber depolarization, covered by an extension of the last Schwann cell and expanded which is carried to the deeper myofibrils by the T-tubules.  Skeletal Muscle 205 TABLE 10–1 Important comparisons of the three types of muscle. C H A P T E R Skeletal Muscle Cardiac Muscle Smooth Muscle 1 0 Muscle Tissue Skeletal Muscle Fibers Single multinucleated cells Aligned cells in branching Single small, closely packed fusiform arrangement cells Cell/fiber shape Cylindrical, 10-100 μm diameter, Cylindrical, 10-20 μm diameter, Fusiform, diameter 0.2-10 μm, length and size many cm long 50-100 μm long 50-200 μm Striations Present Present Absent Location of nuclei Peripheral, adjacent to sarcolemma Central Central, at widest part of cell T tubules Center of triads at A-I junctions In dyads at Z discs Absent; caveolae may be functionally similar Sarcoplasmic Well-developed, with two terminal Less well-developed, one small Irregular smooth ER without reticulum (SR) cisterns per sarcomere in triads with terminal cistern per sarcomere in distinctive organization T tubule dyad with T tubule Special structural Very well-organized sarcomeres, SR, Intercalated discs joining cell, with Gap junctions, caveolae, dense bodies features and transverse tubule system many adherent and gap junctions Control of Troponin C binds Ca2+, moving Similar to that of skeletal muscle Actin-myosin binding occurs with contraction tropomyosin and exposing actin for myosin phosphorylation by MLCK myosin binding triggered when calmodulin binds Ca2+ Connective tissue Endomysium, perimysium, and Endomysium; subendocardial and Endomysium and less-organized CT organization epimysium subpericardial CT layers sheaths Major locations Skeletal muscles, tongue, diaphragm, Heart Blood vessels, digestive and eyes, and upper esophagus respiratory tracts, uterus, bladder, and other organs Key function Voluntary movements Automatic (involuntary) pumping of Involuntary movements blood Efferent Motor Autonomic Autonomic innervation Contractions All-or-none, triggered at motor end All-or-none, intrinsic (beginning at Partial, slow, often spontaneous, plates nodes of conducting fibers) wavelike and rhythmic Cell response to Hypertrophy (increase in fiber size) Hypertrophy Hypertrophy and hyperplasia increased load (increase in cell/fiber number) Capacity for Limited, involving satellite cells Very poor Good, involving mitotic activity of regeneration mainly muscle cells › › MEDICAL APPLICATION Skeletal Muscle Fiber Types Dystrophin is a large actin-binding protein located just Skeletal muscles such as those that move the eyes and eyelids inside the sarcolemma of skeletal muscle fibers which need to contract rapidly, while others such as those for bodily is involved in the functional organization of myofibrils. posture must maintain tension for longer periods while resist- Research on Duchenne muscular dystrophy revealed that ing fatigue. These metabolic differences are possible because of mutations of the dystrophin gene can lead to defective link- varied expression in muscle fibers of contractile or regulatory ages between the cytoskeleton and the extracellular matrix protein isoforms and other factors affecting oxygen delivery (ECM). Muscle contractions can disrupt these weak linkages, and use. Different types of fibers can be identified on the basis causing the atrophy of muscle fibers typical of this disease. of (1) their maximal rate of contraction (fast or slow fibers) and (2) their major pathway for ATP synthesis (oxidative 206 CHAPTER 10 Muscle Tissue FIGURE 10–14 Sensory receptors associated with skeletal muscle. SC MA MF MF MF Capsule MF SC Muscle spindle Intrafusal muscle fibers C Stretch receptor b Afferent nerve fibers Extrafusal (a) The diagram shows both a muscle spindle and a tendon muscle organ. Muscle spindles have afferent sensory and efferent fiber motor nerve fibers associated with the intrafusal fibers, which are modified muscle fibers. The size of the spindle is exagger- ated relative to the extrafusal fibers to show better the nuclei packed in the intrafusal fibers. Both types of sensory receptors provide the CNS with information concerning degrees of stretch and tension within the musculoskeletal system. (b) A TEM cross section near the end of a muscle spindle shows the capsule (C), lightly myelinated axons (MA) of a sensory Golgi tendon nerve, and the intrafusal muscle fibers (MF). These thin fibers organ differ from the ordinary skeletal muscle fibers in having very few myofibrils. Their many nuclei can either be closely aligned Tendon (nuclear chain fibers) or piled in a central dilation (nuclear bag a fibers). Muscle satellite cells (SC) are also present within the external lamina of the intrafusal fibers. (X3600) phosphorylation or glycolysis). Fast versus slow rates of fiber Fast glycolytic fibers are specialized for rapid, short- contraction are due largely to myosin isoforms with different term contraction, having few mitochondria or capil- maximal rates of ATP hydrolysis. laries and depending largely on anaerobic metabolism Histochemical staining is used to identify fibers with dif- of glucose derived from stored glycogen, features that fering amounts of “fast” and “slow” ATPases (Figure 10–15). make such fibers appear white. Rapid contractions lead Other histological features reflecting metabolic differences to rapid fatigue as lactic acid produced by glycolysis among muscle fibers include the density of surrounding capil- accumulates. laries, the number of mitochondria, and levels of glycogen and Fast oxidative-glycolytic fibers have physiological and myoglobin, a globular sarcoplasmic protein similar to hemo- histological features intermediate between those of the globin which contains iron atoms and allows for O2 storage. other two types. Each of these features exists as a continuum in skeletal Table 10–2 summarizes these and other characteris- muscle fibers, but fiber diversity is divided into three major tics of the three skeletal muscle fiber types. The metabolic types: type of each fiber is determined by the rate of impulse con- Slow oxidative muscle fibers are adapted for slow con- duction along its motor nerve supply, so that all fibers of a tractions over long periods without fatigue, having many motor unit are similar. Most skeletal muscles receive motor mitochondria, many surrounding capillaries, and much input from multiple nerves and contain a mixture of fiber myoglobin, all features that make fresh tissue rich in types (Figure 10–15). Determining the fiber types in needle these fibers dark or red in color. biopsies of skeletal muscle helps in the diagnosis of specific  Cardiac Muscle 207 FIGURE 10–15 Skeletal muscle fiber types. › CARDIAC MUSCLE C H A P T E R During embryonic development mesenchymal cells around the primitive heart tube align into chainlike arrays. Rather than fusing into multinucleated cells/fibers as in developing skeletal muscle fibers, cardiac muscle cells form complex junctions between interdigitating processes (Figure 10–16). Cells within one fiber o%en branch and join with cells in adja- 1 0 cent fibers. Consequently, the heart consists of tightly knit bundles of cells, interwoven in spiraling layers that provide for a characteristic wave of contraction that resembles wringing Muscle Tissue Cardiac Muscle out of the heart ventricles. Mature cardiac muscle cells are 15-30 μm in diameter and 85-120 μm long, with a striated banding pattern compa- rable to that of skeletal muscle. Unlike skeletal muscle, how- ever, each cardiac muscle cell usually has only one nucleus and is centrally located. Surrounding the muscle cells is a SO delicate sheath of endomysium with a rich capillary network. A thicker perimysium separates bundles and layers of muscle SO fibers and in specific areas (described in Chapter 11) forms larger masses of fibrous connective tissue comprising the SO “cardiac skeleton.” A unique characteristic of cardiac muscle is the presence of transverse lines that cross the fibers at irregular intervals where the myocardial cells join. These intercalated discs FG SO represent the interfaces between adjacent cells and consist FG of many junctional complexes (Figures 10–16). Transverse regions of these irregular, steplike discs are composed of FG many desmosomes and fascia adherens junctions, which together provide strong intercellular adhesion during the cells’ FOG constant contractile activity. The less abundant, longitudinally oriented regions of each intercalated disc run parallel to the myofibrils and are filled with gap junctions that provide ionic continuity between the cells. These regions serve as “elec- FOG trical synapses,” promoting rapid impulse conduction through FOG many cardiac muscle cells simultaneously and contraction of many adjacent cells as a unit. The structure and function of the contractile apparatus in cardiac muscle cells are essentially the same as in skeletal muscle (Figure 10–17). Mitochondria occupy up to 40% of the cell volume, higher than in slow oxidative skeletal muscle Cross section of a skeletal muscle stained histochemically for fibers. Fatty acids, the major fuel of the heart, are stored as myosin ATPase at acidic pH, which reveals activity of the “slow” triglycerides in small lipid droplets. Glycogen granules as ATPase and shows the distribution of the three main fiber well as perinuclear lipofuscin pigment granules may also be types. Slow oxidative (SO) or type I fibers have high levels of acidic ATPase activity and stain the darkest. Fast glycolytic (FG) present. or type IIb fibers stain the lightest. Fast oxidative-glycolytic Muscle of the heart ventricles is much thicker than that (FOG) or type IIa fibers are intermediate between the other of the atria, reflecting its role in pumping blood through the two types (X40). ATPase histochemistry of unfixed, cryostat cardiovascular system. T-tubules in ventricular muscle fibers section, pH 4.2. are well-developed, with large lumens and penetrate the sarco- plasm in the vicinity of the myofibrils’ Z discs. In atrial muscle T-tubules are much smaller or entirely absent. Sarcoplasmic myopathies (myo + Gr. pathos, suffering), motor neuron reticulum is less well-organized in cardiac compared to skel- diseases, and other causes of muscle atrophy. Different fiber etal muscle fibers. The junctions between its terminal cisterns types also exist in cardiac muscle at various locations within and T-tubules typically involve only one structure of each the heart and in smooth muscle of different organs. type, forming profiles called dyads rather than triads in TEM 208 CHAPTER 10 Muscle Tissue TABLE 10–2 Major characteristics of skeletal muscle fiber types. Fast, Oxidative-Glycolytic Fast, Glycolytic Slow, Oxidative Fibers (Type I) Fibers (Type IIa) Fibers (Type IIb) Mitochondria Numerous Numerous Sparse Capillaries Numerous Numerous Sparse Fiber diameter Small Intermediate Large Size of motor unit Small Intermediate Large Myoglobin content High (red fibers) High (red fibers) Low (white fibers) Glycogen content Low Intermediate High Major source of ATP Oxidative phosphorylation Oxidative phosphorylation Anaerobic glycolysis Glycolytic enzyme activity Low Intermediate High Rate of fatigue Slow Intermediate Fast Myosin-ATPase activity Low High High Speed of contraction Slow Fast Fast Typical major locations Postural muscles of back Major muscles of legs Extraocular muscles sections. Components of this cardiac muscle transverse tubule system have the same basic functions as their counterparts in fish and amphibians, as well as newborn mice, do form new skeletal muscle fibers. muscle when the heart is partially removed, despite the lack Cardiac muscle fiber contraction is intrinsic and sponta- of satellite cells. Research on the possibility of mammalian neous, as evidenced by the continued contraction of the cells heart muscle regeneration builds on work with the animal in tissue culture. Impulses for the rhythmic contraction (or models, focusing primarily on the potential of mesenchymal heartbeat) are initiated, regulated, and coordinated locally by stem cells to form new, site-specific muscle. nodes of unique myocardial fibers specialized for impulse gen- eration and conduction, which are discussed in Chapter 11. As with skeletal muscle fibers, contraction of individual myo- cardial fibers is all-or-none. The rate of contraction is modified by autonomic innervation at the nodes of conducting cells, › SMOOTH MUSCLE with the sympathetic nerve supply accelerating and the para- Smooth muscle is specialized for slow, steady contraction sympathetic supply decreasing the frequency of the impulses. under the influence of autonomic nerves and various hor- Secretory granules about 0.2-0.3 μm in diameter are mones. This type of muscle is a major component of blood found near atrial muscle nuclei and are associated with small vessels and of the digestive, respiratory, urinary, and repro- Golgi complexes (Figure 10–17b). These granules release the ductive tracts and their associated organs. Fibers of smooth peptide hormone atrial natriuretic factor (ANF) that acts on muscle (also called visceral muscle) are elongated, tapering, target cells in the kidney to affect Na+ excretion and water bal- and unstriated cells, each of which is enclosed by an external ance. The contractile cells of the heart’s atria thus also serve an lamina and a network of type I and type III collagen fibers endocrine function. comprising the endomysium (Figure 10–18). Key features of cardiac muscle cells, with comparisons to Smooth muscle cells range in length from 20 μm in small those of skeletal muscle, are summarized in Table 10–1. blood vessels to 500 μm in the pregnant uterus. At each cell’s central, broadest part, where its diameter is 5-10 μm, is a single elongated nucleus. The cells stain uniformly along their lengths, and close packing is achieved with the narrow ends of each › › MEDICAL APPLICATION cell adjacent to the broad parts of neighboring cells. With this The most common injury sustained by cardiac muscle is that arrangement cross sections of smooth muscle show a range of due to ischemia, or tissue damage due to lack of oxygen cell diameters, with only the largest profiles containing a nucleus when coronary arteries are occluded by heart disease. Lack- (Figures 10–18 and 10–19a). All cells are linked by numerous ing muscle satellite cells, adult mammalian cardiac muscle gap junctions. The borders of the cell become scalloped when has little potential to regenerate after injury. However, certain smooth muscle contracts and the nucleus becomes distorted (Figure 10–20). Concentrated near the nucleus are mitochondria, FIGURE 10–16 Cardiac muscle. C H A P T E R Openings of (a) Intercalated disc transverse tubules Intercalated disc Desmosome 1 0 Muscle Tissue Smooth Muscle Gap junction Cardiac muscle cell Sarcolemma Nucleus Mitochondrion Myofibril N F S N I M D I I N b c (a) The diagram of cardiac muscle cells indicates their characteris- spaced intercalated discs (I) that cross the fibers. These irregular tic features. The fibers consist of separate cells in a series joined at intercalated discs should not be confused with the repetitive, interdigitating regions called the intercalated discs, which cross much more closely spaced striations (S), which are similar to those an entire fiber between two cells. The transverse regions of the of skeletal muscle but less well-organized. Nuclei of fibroblasts in steplike intercalated disc have abundant desmosomes and other endomysium are also present. (X200; H&E) adherent junctions for firm adhesion, while longitudinal regions of (c) TEM showing an electron-dense intercalated disc with a step- the discs are filled with gap junctions. like structure along the short interdigitating processes of adjacent Cardiac muscle cells have central nuclei and myofibrils that are cardiac muscle cells. As shown here transverse disc regions have usually sparser and less well-organized than those of skeletal muscle. many desmosomes (D) and adherent junctions called fascia Also, the cells are often branched, allowing the muscle fibers to inter- adherentes (F) which join the cells firmly. Other regions of the disc weave in a more complicated arrangement within fascicles that pro- have abundant gap junctions which join the cells physiologically. duces an e&cient contraction mechanism for emptying the heart. The sarcoplasm has numerous mitochondria (M) and myofibrillar (b) Light microscopy of cardiac muscle in longitudinal section structures similar to those of skeletal muscle but slightly less orga- show nuclei (N) in the center of the muscle fibers and widely nized. (X31,000) 210 CHAPTER 10 Muscle Tissue FIGURE 10–17 Cardiac muscle ultrastructure. D G M D SR a b (a) TEM of cardiac muscle shows abundant mitochondria (M) and in the left atrium and the ventricles. The atrial granules contain rather sparse sarcoplasmic reticulum (SR) in the areas between the precursor of a polypeptide hormone, atrial natriuretic factor myofibrils. T-tubules are less well-organized and are usually associ- (ANF). ANF targets cells of the kidneys to bring about sodium and ated with one expanded terminal cistern of SR, forming dyads (D) water loss (natriuresis and diuresis). This hormone thus opposes rather than the triads of skeletal muscle. Functionally, these struc- the actions of aldosterone and antidiuretic hormone, whose effects tures are similar in these two muscle types. (X30,000) on kidneys result in sodium and water conservation. (X10,000) (b) Muscle cells from the heart atrium show the presence of (Figure 10–17b, used with permission from Dr J. C. Nogueira, membrane-bound granules (G), mainly aggregated at the nuclear Department of Morphology, Federal University of Minas Gerais, Belo poles. These granules are most abundant in muscle cells of the Horizonte, Brazil.) right atrium (~600 per cell), but smaller quantities are also found polyribosomes, RER, and vesicles of a Golgi apparatus. The short dense bodies which contain (-actinin and are functionally plasmalemma invaginations resembling caveolae are o%en similar to the Z discs of striated and cardiac muscle. Smooth numerous at the surface of smooth muscle cells. muscle cells also have an elaborate array of 10-nm intermedi- The fibers have rudimentary sarcoplasmic reticulum, but ate filaments, composed of desmin, which also attach to the lack T-tubules; their function is unnecessary in these smaller, dense bodies. The submembranous dense bodies include cad- tapering cells with many gap junctions. Caveolae of smooth herins of desmosomes linking adjacent smooth muscle cells. muscle cells contain the major ion channels that control Ca2+ Dense bodies in smooth muscle cells thus serve as points for release from sarcoplasmic cisternae at myofibrils which ini- transmitting the contractile force not only within the cells, but tiates contraction. The characteristic contractile activity of also between adjacent cells (Figure 10–20). The endomysium smooth muscle is generated by myofibrillar arrays of actin and other connective tissue layers help combine the force gen- and myosin organized somewhat differently from those of erated by the smooth muscle fibers into a concerted action, for striated muscle. In smooth muscle cells bundles of thin and example peristalsis in the intestine. thick myofilaments crisscross the sarcoplasm obliquely. The Smooth muscle is not under voluntary motor control and myosin filaments have a less regular arrangement among the its fibers typically lack well-defined neuromuscular junctions. thin filaments and fewer crossbridges than in striated muscle. Contraction is most commonly stimulated by autonomic Moreover smooth muscle actin filaments are not associated nerves, but in the gastrointestinal tract smooth muscle is also with troponin and tropomyosin, using instead calmodulin controlled by various paracrine secretions and in the uterus by and Ca2+-sensitive myosin light-chain kinase (MLCK) to oxytocin from the pituitary gland. produce contraction. The contraction mechanism, however, is Axons of autonomic nerves passing through smooth basically similar to that in striated muscle. muscle have periodic swellings or varicosities that lie in close As shown in Figure 10–20 the actin myofilaments insert contact with muscle fibers. Synaptic vesicles in the vari- into anchoring cytoplasmic and plasmalemma-associated cosities release a neurotransmitter, usually acetylcholine or  Smooth Muscle 211 FIGURE 10–18 Smooth muscle. C H A P T E R XS 1 0 IC Muscle Tissue Smooth Muscle OL P LS a b Cells or fibers of smooth muscle are long, tapering structures with elongated nuclei centrally located at the cell’s widest part. (a) In most of the digestive tract and certain similar structures smooth muscle is organized into two layers which contract in a coordinated man- A ner to produce a wave that moves the tract’s contents in a process termed peristalsis. In smooth muscle of the small intestine wall cut in cross section, cells of the inner circular (IC) layer are cut lengthwise and cells of the outer longitudinal layer (OL) are cut transversely. Only some nuclei (arrows) of the latter cells are in the plane of section, so that many cells appear to be devoid of nuclei. (X140; H&E) (b) Section of smooth muscle in bladder shows interwoven bundles of muscle fibers in cross section (XS) and longitudinal section (LS) with the same fascicle. There is much collagen in the branching perimysium (P), but the endomysium can barely be seen by routine staining. (X140; Mallory trichrome) (c) Section stained only for reticulin reveals the thin endomysium around each fiber, with more reticulin in the connective tissue of small arteries (A). Reticulin fibers associated with the basal laminae of smooth muscle cells c help hold the cells together as a functional unit during the slow, rhythmic contractions of this tissue. (X200; Silver) norepinephrine, which diffuses and binds receptors in the Key histologic and functional features of smooth muscle, sarcolemmae of numerous muscle cells. There is little or no with comparisons to those of skeletal and cardiac muscle, are specialized structure to such junctions. As in cardiac muscle, summarized in Table 10–1. stimulation is propagated to more distant fibers via gap junc- tions which allow all the smooth muscle cells to contract syn- chronously or in a coordinated manner. In addition to contractile activity, smooth muscle cells also › › MEDICAL APPLICATION supplement fibroblast activity, synthesizing collagen, elastin, and Benign tumors called leiomyomas commonly develop from proteoglycans, with a major influence on the extracellular matrix smooth muscle fibers but are seldom problematic. They (ECM) in tissues where these contractile cells are abundant. Active most frequently occur in the wall of the uterus, where they synthesis of ECM by the small cells/fibers of smooth muscle may are more commonly called fibroids and where they can reflect less specialization for strong contractions than in skeletal become su&ciently large to produce painful pressure and and cardiac muscle and is similar to this synthetic function in unexpected bleeding. other contractile cells, such as myofibroblasts and pericytes. FIGURE 10–19 Smooth muscle ultrastructure. M N DB M C a b N (a) TEM of a transverse section of smooth muscle showing several (b) Longitudinal section showing several dense bodies (DB) in cells sectioned at various points along their lengths, yielding profiles the cytoplasm and at the cell membrane. Thin filaments and of various diameters with only the largest containing a nucleus. Thick intermediate filaments both attach to the dense bodies. In the and thin filaments are not organized into myofibril bundles, and cytoplasm near the nucleus (N) are mitochondria, glycogen gran- there are few mitochondria (M). There is evidence of a sparse external ules, and Golgi complexes. In the lower right corner of the photo lamina around each cell, and reticular fibers are abundant in the ECM. the cell membrane shows invaginations called caveolae (C) that A small unmyelinated nerve (N) is also seen between the cells. (X6650) may regulate release of Ca2+ from sarcoplasmic reticulum. (X9000) FIGURE 10–20 Smooth muscle contraction. Thick filaments Thin filaments Dense body Adjacent cells physically coupled at dense bodies CT Nucleus C Dense body a