Muscle Tissue PDF

MUSCLE TISSUE: Consists of cells that optimize the universal cell property of contractility. As in all cells, actin microfilaments and associated proteins generate the forces necessary for muscle contraction, which drives movement within organ systems, of blood, and of the body as a whole. All muscl...

MUSCLE TISSUE: Consists of cells that optimize the universal cell property of contractility. As in all cells, actin microfilaments and associated proteins generate the forces necessary for muscle contraction, which drives movement within organ systems, of blood, and of the body as a whole. All muscle cells originate from embryonic mesoderm and differentiate by elongation and abundant synthesis of the myofibrillar proteins actin and myosin. Three different types of muscle tissue: - Skeletal muscle: contains bundles of very long, multinucleated cells with cross-striations and produces quick, forceful contractions, usually under voluntary control. - Cardiac muscle: also has cross-striations, but less elongated, often branched cell bound to one another at structures called intercalated discs, unique to cardiac muscle. Contraction is involuntary, vigorous and rhytmic - Smooth muscle: comprises collections of fusiform cells, which lack striations and generate slow, involuntary contractions In all of them, contraction involves sliding interaction of touch myosin filaments along thin actin filaments. The forces necessary for this sliding are generated by other proteins affecting the weak interactions in the bridges between actin and myosin. The cytoplasm of muscle cells often becomes sacroplasm, smooth ER is in the sacroplasmic reticulum, and the muscle cell membrane is called the sarcolemma Medical application: Exercise enlarges the skeletal musculature by stimulating formation of new myofibrilis and growth in the diameter of individual muscle fibers - hypertrophy. Tissue growth by an increase in the number of cells is called hyperplasia, which takes place very readily in smooth muscle, where cells have not lost the capacity to divide by mitosis. Skeletal muscle: Also called striated muscle, consist of muscle fibers, which are long, cylindrical multinucleated cells. During embryonic skeletal muscle development, mesenchymal myoblasts fuse to form multinucleated myotubes, each surrounded and bound by an external (or basal) lamina. Myotubes then mature further as striated muscle fibers. The contractile apparatus begins to fill the sacroplasm, while nuclei elongate and localize peripherally just under the sacrolemma, a nuclear site unique to skeletal muscle fibers. A small population of reserve progenitor cells called muscle satellite cells remains adjacent to most fibers of mature skeletal muscle, between the sacrolemma and the external lamina. Satellite cells proliferate and produce new muscle fibers following muscle injury Organization of skeletal muscle: Thin layers of connective tissue surround and organize the contractile fibers, becoming well-developed in skeletal muscle. - The epimysium, an external sheath of dense irregular connective tissue, surrounds the entire muscle. Septa of this tissue extend inward, carrying the larger nerves, blood vessels and lymphatics of the muscle - The perimysium occurs as a thin connective tissue layer immediately surrounding each bundle of muscle fibers termed a fascicle. A fascicle of muscle fibers makes up a functional unit in which the fibers work together most efficiently. Nerves, blood vessels and lymphatics penetrate the perimysium to supply each fascicle. - Within each fascicle a very thin, delicate layer of reticular fibers and scattered fibroblasts, the endomysium, envelops the external lamina of individual muscle fibers. - Tendons develop together with skeletal muscles and join muscles to the periosteum of bones. Collagen in the external lamina and these connective tissue layers serves to transmit the mechanical forces generated by the contracting muscle fibers, and individual muscle fibers seldom extend from one end of a muscle to the other All three layer plus the dense irregular connective tissue of the deep fascia, which overlies the epimysium, have continuity with the dense regular connective tissue of a tendon at myotendinous junctions, which join a muscle to bone, skin, or another muscle. Organization within muscle fibers Longitudinally sectioned skeletal muscle fibers display strations of alternating light and dark bands. The highly organized sacroplasm consists largely of long cylindrical filament bundles called myofibrilis running parallel to the fibers long axis. The dark stripes on the myofibrils comprise the A bands (anisotropic in polarized light microscopy), the light light ones are the I bands (isotropic, do not alter polarized light). In TEM each band appears bisected by a darker transverse line, the Z disc. The functional subunit of the myofibril is the sacromere, the force-generating and load-bearing apparatus of muscle fibers. Sacromeres extend from Z disc to Z disc. Mycrofibrils consists of an end-to-end repetitive arrangement of sacromeres, with a sacroplasmic reticulum and most other organelles located between the myofibrils. Molecules composing thin and thick filaments: Myofilaments, which include both thick and thin filaments, consists of contractile protein arrays bundled within myofibrils. - A thick myofilament, contains 200-500 molecules of myosin - A thin filament contains F-actin, tropomyosin and troponin. The A and I banding pattern of sacromeres is due mainly to the regular arrangement of thick and thin myofilaments, composed of myosin and F-actin. Each myofibril comprises thousands of symmetrically arranged thick and thin myofilaments. The thick occupy the A band at the middle region of the sacromere. Myosin, a large protein complex, has two identical heavy chains and two pairs of light chains. Myosin heavy chains are thin, rodlike motor proteins twisted together as the myosin tails. The myosin head contain binding sites for actin, to form transient crossbridged between the thick and thin filaments, and for ATP catalyzing energy release. Several hundred myosin complexes make up each thick filament, arranged with their rodlike portions aligned and their globular heads directed toward either end. The thin, double helical F-actin filaments run between the thick. The G-actin monomers comprising these filaments each contain a binding site for myosin. The thin filaments also have two tightly associated regulatory proteins: - Tropomyosin: with a coil of two polypeptide chains located in the groove between the two twisted actin strands - Troponin: a complex of three subunits: TnT, which attaches to tropomyosin TnC, which binds ca2+ TnI, which regulates the actin-myosin interaction > Troponin complexes attach at specific sites regularly spaced along each tropomyosin molecule Actin-filaments are anchored on the Z disc by the actin-binding protein a-acitinin, and exhibit opposite polarity on each side of this disc. An important accessory protein in I bands is titin, the largest protein in the body. Titin supports the ends of thick myofilaments and connects them to the Z disc. Nebulin, binds each thin myofilament laterally and helps anchor them to a-acitinin and specifies the length of the actin polymers during myogenesis. The A bands contain both the thick filaments and the overlapping portions of thin filaments. A bands have a lighter middle layer called H zone, which corresponds to a region with only the rodlike portions of the myosin molecules and no thin filaments. Bisecting the H zone is the M line, containing a myosin-binding protein myomesin that holds the thick filaments in place, and creatine kinase. This enzyme catalyzes the transfer of phosphate groups from phosphocreatine, a storage form of high-energy phosphate groups, to ADP, helping to supply ATP for muscle contraction. Myosin and actin represent over half of the total protein in striated muscle. The overlapping arrangement of thin and thick filaments within sacromeres produce in TEM cross sections, hexagonal patterns of structures, which were important in determining the functional organization of the filaments and other proteins in the myofibril. Sacroplasmic reticulum & transverse tubule system: In the skeletal muscle fibers, the membraneous smooth ER, called the sarcoplasmic reticulum, contains pumps and other proteins for Ca2+ sequestration and surrounds the myofibrils. Calcium release from cisternae of the sacroplasmic reticulum through voltage-gated Ca2+ channels is triggered by membrane depolarization produced by a motor nerve Organization of a skeletal muscle fiber: Consist mainly of myofibrils. Each myofibrils extends the length of the fiber, surrounded by parts of the sacroplasmic reticulum. The sacrolemma has deep invaginations called T-tubules, each of which becomes associated with two terminal cisternae of the sacroplasmic reticulum. T-tubules and cisternaes comprise a ‘’triad’’ of small spaces along the surface of the myofibrils. Triggering simultaneous Ca2+ release from sacroplasmic reticulum throughout the muscle fiber to produce uniform contraction of all myofibrils depends on long tubular infoldings of the sacrolemma called transverse or T-tubules. These invaginations penetrate deeply into the sacroplasm and encircle each myofibril near the aligned A and I band boundaries of sacromeres. Mechanism of contraction: Neither the thick or the thin filaments change their length during this process. Contraction occurs as the overlapping thin and thick filaments of each sacromere slide past one another. Contraction is induced when an action potential arrives at synapse, the neuromuscular junction, and is transmitted along the T-tubules to terminal cisternae of the sacroplasmic reticulum to trigger Ca2+ release. In a resting muscle the myosin heads cannot bind actin because the binding sites are blocked by the troponin-trypomyosin complex on the F-actin filaments. Calcium ions released upon neural stimulation bind troponin changing its shape and moving tropomyosin on the F-actin to expose the myosin-binding active sites and allow crossbridges to form. Binding actin produces a conformational change or pivot in the myosins, which pulls the thin filaments farther into the A band, towards the Z disc. Energy from myosin head pivot that pulls actin comes from hydrolysis of ATP bound to the myosin heads, after which myosin binds another ATP and detaches from actin. In the continued presence of Ca2+ and ATP, these attach-pivot-detach events occur in repeating cycles, each about 50 milliseconds, which rapidly shorten the sacromere and contract the muscle. A single contraction results from hundreds of these cycles. When the neural impulse stops and levels of free Ca2+ ions diminish, trypomyosin again covers the myosin-binding sites on actin and the filaments passively slide back and sacromeres return to their relaxed length. In the complete absence of ATP, the actin-myosin crossbridges become stable, which accounts for the rigidity of skeletal muscles (rigor mortis) that occurs as mitochondrial activity stops after death. Innervation: Myelinated motor nerves branch out within the perimysium, where each nerve gives rise to several unmyenilated terminal twigs that penetrate the endomysium and form synapses with individual muscle fibers. Schwann cells enclose the smalls axon branches and cover their points of contact with the muscle cells; the external lamina of Schwann cells fuses with that on the sacrolemma. Each axonal branch forms a dilated termination situated within a trough on the muscle cell surface forming part of the synapses termed neuromuscular junctions or motor end plates (MEPs). As in all, synapses, the axon terminal contains mitochondria and numerous synaptic vesicles, here the vesicles contain the neurotransmitter acetylcholine. A synaptic cleft lies between axon and muscle in these junctions. adjacent to the synaptic cleft, the sacrolemma is thrown into numerous deep junctional folds which provide for greater postsynaptic surface area and more transmembrane acetylcholine receptors. When a nerve action potential reaches MEP, acetylcholine is liberated from the axon terminal, diffuses across the cleft, and binds to its receptors in the folded sacrolemma. The acetylcholine receptor contains a nonselective cation channel that opens upon neurotransmitter binding, allowing influx of cations, depolarizing the sacrolemma, and producing the muscle action potential. Acetylcholine quickly dissasociates from its receptors, and free neurotransmitter is removed from the synaptic cleft by the extracellular enzyme acetylchollinesterase, preventing prolonged contact of the transmitter with its receptors. An axon from a single motor neuron can form MEPs with one or many muscle fibers. Innervation of single muscle fibers by single motor neurons provides precise control of muscle activity and occurs. Larger muscles with coarser movements have motor axons that typically branch profusely and innervate 100 or more muscle fibers. The single axon and all the muscle fibers in contact with its branches make up a motor unit. Individual striated muscle fibers do not show graded contraction - they contract either all the way or not at all. To vary the force of contraction, the fibers within a muscle fascicle do not all contract at the same time. With large muscles composed of many motor units, the firing of a single axon will generate tension proportional to the number of muscle fibers it innervates. Therefore, the number of motor units and their size controls the intensity and precision of a muscle contraction. Medical application: Myasthenia gravis is an autoimmune disorder that involves circulating antibodies against proteins of acetylcholine receptors. Antibody binding to the antigenic sites interferes with acetylcholine activation of their receptors, leading to intermittent period of skeletal weakness. As the body attempts to correct the condition, junctional folds of sacrolemma with affected receptors are internalized, digested by lysosomes, and replaced by newly formed receptors. These receptors, however, are again made unresponsive to acetylcholine by similar antibodies, and the disease follows a progressive course. The extraocular muscles of the eyes are commonly the first affected. Muscle spindles & tendon organs Striated muscles and myotendinous junctions contain sensory receptors that act as propioceptors, providing the CNS with data from the muculoskeletal system. Among the muscle fascicles are stretch detectors known as muscle spindles. A muscle spindle is encapsulated by modified perimysium, with concentric layers of flattened cells, containing interstitial fluid and a few thin muscle fibers filled with nuclei and called intrafusal fibers. Several sensory nerve axons penetrate each muscle spindle and wrap individual intrafusal fibers. Muscle spindles detect changes in length (distension) of the surrounding (extrafusal) muscle fibers caused by body movements and the senory nerves relay this information to the spinal cord. Different types of sensory and intrafusal fibers mediate reflexes of varying complexity to help maintain posture and to regulate the activity of opposing muscle groups involved in motor activities such as walking. Muscle spindles have afferent sensory and efferent motor nerve fibers associated with modified muscle fibers called intrafusal fibers. Intrafusal fibers differ from the ordinary skeletal muscle fibers in having very few myofibrils. Their many nuclei can either be closely aligned (nuclear chain fibers) or piled in a central dilation (nuclear bag fibers). Muscle satellite cells also occur within the external lamina of the intrafusal fibers. A similar role is played in myotendenous junctions by Golgi tenon organs, much smaller encapsulated structures that enclose sensory axons penetrating among the collagen bundles. Tendon organs detect changes in tension within tendons produced by muscle contraction and act to inhibit motor nerve activity if tension becomes excessive. Both propioceptors detect increase in tension so they help regulate the amount of effort required to perform movements that call for variable amounts of muscular force. Medical application: Dystrophin is a large actin-binding protein located just inside the sacrolemma of skeletal muscle fibers, which is involved in the functional organization of myofibrils. Research on Duchenne muscular dystrophy reveals that mutations of the dystrophin gene can lead to defective linkages between the cytoskeleton and ECM. Muscle contractions can disrupt these weak linkages, causing the atrophy of muscle fibers typical of this disease Skeletal muscle fiber types: Skeletal muscles such as those that move the eyes and eyelids need to contract rapidly, while others such as those for bodily posture must maintain tension for longer periods while resisting fatigue. These metabolic differences are possible because of varied expression in muscle fiber types utilizes: 1. their maximal rate of contraction (fast or slow) 2. their major pathway for ATP synthesis (oxidative phosphorylation or glycolysis) Fast or slow rates of fiber contraction are due largely to myosin isoforms with different maximal rates of ATP hydrolysis. Myoglobin is a globular sacroplasmic protein similar to hemoglobin that contains iron atoms and allows for O2 storage. Skeletal muscle fibers types: - Slow oxidative muscle fibers: adapted for slow contractions over long period without fatigue, have many mitochondria, many surrounding capillaries, and much myoglobin, all features that make fresh tissue rich in these fibers dark or red in color - Fast glycolytic fibers are specialized for rapid, short-term contraction, having few mitochondria or capillaries and depending largely on anaerobic metabolism of glucose derived from stored glycogen, features which make such fibers appear white. Rapid contractions lead to rapid fatigue as lactic acid produced by glycolysis accumulates. - Fast oxidative-glycolyctic fibers have physiological and histological features intermediate between the other two types, Cardiac muscle: When during embryonic development, the mesenchymal cells around the primitive heart tube line up into chainlike arrays, and instead of fusing into multinucleated cells/fibers as in developing skeletal muscle, the aligned cardiac muscle cells form fibers having complex cell-cell junctions with abundant interdigiating processes. Their fibers consist of separate cells joined in a series at the intercalated discs, which is revealed to have step-like structures in the TEM. The transverse regions of the discs are highly interdigitated and have abundant desmosomes and other adherent junctions for firm adhesion, while longitudinal regions of the discs have numerous gap junctions. The transverse regions are highly interdigiated and contain many desmosomes and adhesive strips called fascia adherens junctions, which together provide strong intercellular adhesion during the cells’ constant contractile activity. The laterally oriented regions of each step-like intercalated disc run parallel to the myofibrils and include numerous gap junctions, which provide ionic continuity between the cells. These regions serve as "electrical synapses’’, promoting rapid impulse conduction through many cardiac muscle cells simultaneously and contraction of many adjacent cells as a unit. Cardiac cell muscles have central nuclei and myofibrils which are usually sparser and less well-organized compared to skeletal muscles. The cells are often branched, allowing the fibers to interweave in a complicated more helical arrangement within fadicles, which helps produce an efficient, wringing contraction mechanism for emptying the heart. Mature cardiac muscle has a striated banding pattern comparable to that of skeletal muscle. But, each cell of the cardiac muscle fiber usually has only one centrally located nucleus. A delicate sheath of endomesityum with a rich capillary network surrounds each fiber. A thicker perimysium separates bundles and layers of cardiac muscle fibers and in specific areas forms a larger mass of fibrous connective tissue comprising the ‘’cardiac skeleton’’. The structure and function of the contractile apparatus in cardiac muscles are essentially the same as in skeletal muscles. Mitochondria occupies up to 40% of the cell volume, higher than in slow oxidative skeletal muscle fibers. Fatty acids, the major fuel of the heart, are stored triglycerides in small lipid droplets. Glycogen granules as well as perinuclear lipofuscin pigment granules may also occur. Cardiac muscle ultrastructure: Abundant mitochondria and rather sparse sacroplasmic reticulum in the areas between myofibrils. T-tubules become less well organized and usually associate with one expanded terminal cistern of SR, forming dyads rather than triads. Muscle cells from the heart atrium show the presence of membrane-bound granules, mainly aggregated at the nuclear poles. These granules occur most abundantly in muscle cells of the right atrium, but smaller quantities also appear in the left atrium and the ventricles. The atrial granules contain the precursor of a polypeptide hormone, atrial natriurectic factor. They target cells of the kidneys to bring about sodium and water loss (natriuresis and diuresis). This hormone then opposes the actions of aldosterone and antidiurectic hormone, whose effects on kidneys result in sodium and water conservation. Muscle of the heart ventricles is much thicker than the one of the atria, reflecting its role in pumping blood through the cardiovascular system. Well-developed T-tubules in ventricular muscle fibers have large lumens and penetrate the sacroplasm in the vicinity of the myofibrils’ Z discs. In atrial muscle, T-tubules are much smaller or entirely absent. Sacroplasmic reticulum is well-organized in cardiac compared to skeletal muscle fibers. The junctions between its terminal cisterns and T-tubules typically involve only one structure of each type, forming profiles called dyads rather than triads. Components of this cardiac muscle transverse tubule system have the same basic functions as their counterparts in skeletal muscle. Cardiac muscle fiber contraction occurs intrinsically and spontaneously, as evidenced by the continued contraction of myocardial cells in tissue culture. As with skeletal muscle fibers, contraction of individual myocardial fibers is all­or­none. Impulses for rhythmic contraction (or heartbeat) are regulated and coordinated locally by nodes of unique myocardial fibers specialized for this activity. Secretory granules release the peptide hormone atrial natriuretic factor (ANF), which acts on target cells in the kidney to affect Na+ excretion and water balance. Thus, contractile cells of the heart’s atria also serve an endocrine function. Medical application: The most common injury sustained by cardiac muscle occurs due to ischemia, lack of oxygen when coronary arteries undergo gradual occlusion during cardiovascular disease. Lacking muscle satellite cells, adult mammalian cardiac muscle has little potential to regenerate after injury. Research on the possibility of mammalian heart muscle regeneration builds on work with the animal models, focusing primarily on the potential of mesenchymal stem cells to form new, site­specific muscle. Smooth muscle: Smooth muscle becomes specialized for slow, steady contraction under the influence of autonomic nerves and various hormones. This type of muscle represents a major component of blood vessels and of the digestive, respiratory, urinary, and reproductive systems. Fibers of smooth muscle (also called visceral muscle) develop as elongated, tapering, and nonstriated cells, each enclosed by an external lamina and a network of type I and type III collagen fibers comprising the endomysium. Cells or fibers of smooth muscle consist of long, tapering structures with elongated nuclei centrally located at the cell’s widest part. In most of the digestive tract and other similar structures smooth muscle becomes organized into two layers which contract in a coordinated manner 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 layer are cut lengthwise, and cells of the outer longitudinal layer are cut transversely. Only some nuclei of the latter cells occur in the plane of section, causing many cells to appear devoid of nuclei. Abundant collagen occurs in the branching perimusium, but the endomysium can barely be seen by routine staining. Smooth muscle - ultrastructure: At each cell’s central, broadest part lies a single elongated nucleus. The cells stain uniformly along their lengths and close packing is achieved with the narrow ends of each cell adjacent to the broad parts of neighboring cells. With this arrangement, cross sections of smooth muscle show a range of cell diameters, with only the largest cell profiles containing nuclei. All adjacent cells/fibers possess abundant gap junctions. The borders of the cell become scalloped when smooth muscle contracts and the nucleus becomes distorted. Mitochondria, polyribosomes, RER, and Golgi apparatus vesicles occur concentrated near the cell nucleus. Smooth muscle cell surfaces often display numerous small plasmalemma invaginations resembling caveolae. Thick and thin filaments do not get organized into myofibril bundles and there are few mitochondria. A sparse external lamina surrounds each cell and dark reticular fibers appear abundantly in the ECM. A small unmyelinated nerve is also seen between the cells. Longitudinal section showing several dense bodies in the cytoplasm and at the cell membrane. Both thin filaments and intermediate filaments attach to the dense bodies. Near the nucleus are mitochondria, glycogen granules, and Golgi complexes. In both photos the cell membranes show invaginations called caveolae with various membrane proteins for cell signaling and for regulating uptake and release of Ca2+ from sarcoplasmic reticulum. Smooth muscle contraction: Most molecules that allow contraction are similar in the three types of muscle, but the contractile filaments of smooth muscle are oriented at oblique angles to the long axis of the cell, resulting in a twisting of the smooth muscle cells during contraction. Thin filaments attach to dense bodies located at the cell membrane and deep in the cytoplasm, with the connection mediated by α­-actinin in the dense bodies. Dense bodies also serve as attachment sites for intermediate filaments and for intercellular adhesive junctions. This arrangement of both the cytoskeleton and contractile apparatus allows the multicellular tissue to contract as a unit, providing better efficiency and force. The fibers have rudimentary sarcoplasmic reticulum but lack T­-tubules, the latter unnecessary in these smaller, tapering cells bearing many gap junctions. The caveolae of smooth muscle cells contain the major ion channels controlling Ca2+ release from sarcoplasmic cisternae that initiates contraction of myofibrils. The characteristic contractile activity of smooth muscle involves myofibrillar arrays of actin and myosin organized differently from those of striated muscle. In smooth muscle cells, bundles of thin and thick myofilaments crisscross the sarcoplasm obliquely. The myosin filaments have a less regular arrangement among the thin filaments and fewer cross bridges than in striated muscle. Moreover, thin filaments of smooth muscle lack troponin and have tropomyosin of uncertain function. Here these proteins are replaced in the contractile apparatus with two others, calmodulin and Ca2+­sensitive myosin light­chain kinase (MLCK). The contraction mechanism itself, however, basically resembles that in striated muscle. The actin myofilaments insert into anchoring cytoplasmic and plasmalemma­associated dense bodies, which contain αactinin and serve functionally like the Z discs of striated and cardiac muscle. The dense bodies include cadherins of desmosomes linking adjacent smooth muscle cells. Dense bodies in smooth muscle cells thus serve as points for transmitting the contractile force not only within the cells, but also between adjacent cells. The endomysium and other connective tissue layers help combine the force generated by the smooth muscle fibers into a concerted action, for example, peristalsis in the intestine. Smooth muscle contraction occurs without voluntary motor control and its fibers typically lack well­defined neuromuscular junctions. Contraction is usually stimulated by autonomic nerves, but in the gastrointestinal tract control of smooth muscle activity also involves various paracrine secretions and in the uterus oxytocin from the pituitary gland. Axons of autonomic nerves passing through smooth muscle have periodic swellings or varicosities that lie in close contact with muscle fibers. Synaptic vesicles in the varicosities release a neurotransmitter, usually acetylcholine or norepinephrine, which diffuses and binds receptors in the sarcolemmae of muscle cells. Little or no specialized structure defines such synaptic junctions. As in cardiac muscle, stimulation is propagated to more distant fibers via gap junctions that allow all the smooth muscle cells to contract synchronously or in a coordinated manner. smooth muscle cells also supplement fibroblast activity, synthesizing collagen, elastin, and proteoglycans, with a major influence on the ECM in tissues with many such cells. Medical application: Benign tumors called leiomyomas commonly develop from smooth muscle fibers but are seldom problematic. They most frequently occur in the wall of the uterus, where they are more commonly called fibroids and where they can become sufficiently large to produce painful pressure and unexpected bleeding. Regeneration of muscle tissue: In skeletal muscle, although the multinucleated cells cannot undergo mitosis, the tissue can still display limited regeneration. The sparse population of mesenchymal satellite cells lying inside the external lamina of each muscle fiber serve as the source of regenerating cells. Satellite cells occur as inactive, reserve myoblasts that persist after muscle differentiation. After injury, the normally quiescent satellite cells become activated, proliferating, and fusing to form new skeletal muscle fibers. A similar activity of satellite cells has been implicated in muscle growth after extensive exercise, a process in which they fuse with existing fibers to increase muscle mass beyond that which occurs by cell/fiber hypertrophy. Following major traumatic injuries, scarring and excessive connective tissue growth interferes with skeletal muscle regeneration. Cardiac muscle lacks satellite cells and shows very little regenerative capacity beyond early childhood. Defects or damage (eg, infarcts) to heart muscle are generally replaced by proliferating fibroblasts and growth of connective tissue, forming only myocardial scars. Smooth muscle, composed of simpler and smaller mononucleated cells, can undertake a more active regenerative response. After injury, viable smooth muscle cells undergo mitosis and replace the damaged tissue. Contractile pericytes from the walls of small blood vessels participate in the repair of vascular smooth muscle.