OBJECTIVES

This chapter should help you to:

· Know the 3 major types of muscle tissue and compare them in terms of structure, function, and location in the body.
· Know the function(s) of muscle tissue and contemplate what measures would have to be taken to sustain life without it.
· Know the relationships between muscle fascicles, muscle fibers, myofibrils, and myofilaments.
· Explain the role of the T tubules and the sarcoplasmic reticulum in striated muscle function.
· Describe the mechanisms of skeletal muscle stimulation, contraction, and relaxation at the molecular, cellular, and tissue levels. · Recognize the type of muscle tissue present in a slide or photomicrograph of an organ and describe its probable function.

I. GENERAL FEATURES OF MUSCLE TISSUE

A. Terminology: Many special terms are applied to muscle. Most include the prefixes sarco- or myo- .

B. Specialization for Contraction: Muscle cells are structurally and functionally specialized for contraction, which requires 2 types of special protein filaments called myofilaments: thin filaments containing actin and thick filaments containing myosin.

C. Mesodermal Origin: Nearly all muscle cells arise from mesoderm. Mesenchymal cells differentiate into muscle cells through a process involving accumulations of myofilaments in the cytoplasm and development of special membranous channels and compartments. Exception: Smooth muscles of the iris arise from ectoderm.

D. Cell Shape: Muscle cells are typically longer than they are wide, sometimes reaching lengths of 4 cm. Muscle cells are therefore often called muscle fibers, or myofibers.

E. Organization: Muscle tissues are groups of muscle cells organized by connective tissue. This arrangement allows the groups to act together or separately, generating mechanical forces of varying strength. Named muscles of the body leg, biceps brachii) are organs made up of highly organized muscle tissue (II.G).

F, Types of Muscle Tissue: The main muscle tissue types are smooth muscle and the 2 types of striated muscle, skeletal and cardiac. Smooth muscle (IV) is found mainly in the walls of hollow organs leg, intestines and blood vessels); its contraction is slow, often in waves, and under involuntary control. In histologic section, it lacks the banding pattern, or striations, seen in the other 2 types. Skeletal muscle (II) is found mainly in association with bones, which act as pulleys and levers to multiply the force of its quick, strong, voluntary contractions. Cardiac muscle (III) is found exclusively in the walls of the heart; its contractions are quick, strong, rhythmic, and involuntary. Characteristics of the different muscle types are summarized in Table 10-1.

II. SKELETAL MUSCLE

A. Histogenesis: Skeletal muscle arises from mesenchyme of mcsodermal origin. The mesenchymal cells retract their long cytoplasmic processes and assume a shortened spindle shape to become myohlasts; these fuse to form multinucleated myotubes, Myotubes elongate by incor porating additional myoblasts while myoflnnrents accumulate in their cytoplasm. Eventually, the accumulated myofilaments organize into myofibrils (II.B.l.c) and displace the nuclei and other cytoplasmic components peripherally.

B, Skeletal MuscleCells: Mature skeletal muscle fibers are elongated, unbranchcd, cylindrical, multinucleated cells. The flattened, peripheral nuclei lie just under the sarcolemma (muscle cell plasma membrane); most of the organelles and sarcoplasm (muscle cell cytoplasm) are near the poles of the nuclei. The sarcoplasm contains many mitochondria, glycogen granules, and an oxygen-binding protein called myoglohin, and it accumulates lipofuscin pigment with age. Mature-skeletal muscle fibers cannot divide.


1.Myofilaments. In skeletal muscle fibers, these are of 2 major types. a. Thin filaments. Thin (actin) filaments (Fig 10-1) have several components. (1) Filamentous actin (F-actin) is a polymeric chain of glohular actin (G-actin) mono- mers. Each thin filament contains 2 of F-actin strands wound in a double helix. (2) Tropomyosin is a long, thin, double-helical polypeptide that wraps around the actin double helix, lies in the grooves on its surface, and spans 7 G-actin monomers. (3) Troponin is a complex of 3 globular proteins. TnT (troponin T) attaches each complex to a specific site on each tropomyosin molecule, TnC binds calcium ions, and TnI inhibits the interaction between the thin and thick filaments. b. Thick filaments. A myosin molecule is a long, golf-club-shaped polypeptide. A thick (myosin) filament is a bundle of myosin molecules with their shafts pointing toward and overlapping in the bundle's middle and their heads projecting from the bundle's ends. This arrangement leaves a headless region in the center of each tilament corresponding to the H band (II.B. I.d). Treating myosin molecules with papain (a proteolytic enzyme) cleaves them, at a point near the head, into 2 pieces. The piece containing most of the thin shaft is termed light meromysin; the head and associated section of the shaft make up heavy meromyosin. The head portion of heavy meromysin has an ATP-binding site and an actin-binding site, both necessary for contraction. c. Organization of the myofilaments. The banding pattern of skeletal muscle (II.B.l.d) reflects the grouping of its myofilaments into parallel bundles of thick and thin filaments called myofibrils. Each muscle fiber map contains several myofibrils, the number depending on its size.

(I) Appearance of the myofibrils in cross section. EM images of myofibrils in cross section reveal patterns of large and small dots corresponding to the thick and thin filaments, respectively. Sections containing both filament types have 6 thin filaments in hexagonal array around each thick filament. Each thick filament shares 2 of its surrounding thin filaments with each adjacent thick filament to form a repeating crystalline pattern (Fig 10-2). (2) Appearance of the myofibrils in longitudinal section. At both light and EM levels, each myofibril exhibits repeating, linearly arranged, functional subunits called sarcomeres, which have bands (striations) running perpendicular to the long axis of the myofibril. The sarcomeres of each myofibril lie in register with those in adjacent myofibrils so that their bands appear continuous. The sarcomere is separated from its neighbors at each end by a dense Z line, or Z disk. A major protein of the Z disk, a-actinin, anchors one end of the thin filaments and helps maintain spatial distribu tion. The thin filaments extend toward the middle of the sarcomere. The center of each sarcomere is marked by the M line, which holds the thick filaments in place. Desmin-containing intermediate filaments are found in both M lines and Z disks. The thick filament bundles lie at the center of each sarcomere, are bisected by the M line, and overlap the free ends of the thin filaments. The pattern of overlapping between the thick and thin filaments is responsible for the banding pattern and differs depend ing on the state of contraction of the myofibrils (Fig 10-2). d. Bands. With the light microscope, skeletal muscle exhibits alternating light- and dark staining bands running perpendicular to the long axis of the muscle fibers. (1) I bands. The light-staining bands contain only thin filaments. They are known as I bands (isotropic) because they do not rotate polarized light. Each I band is bisected by a Z line. Thus each sarcomere has 2 half  I bands, one at each end (Fig 10-2). (2) A bands, One dark-staining band lies in the middle of each sarcomere and shows the position of the thick filament bundles. This is known as an A band (anisotropic) because it is birefringent (rotates polarized light). At the EM level, each A band has a lighter-staining central region termed the H band, which is bisected by an M line. The H band lies between the free ends of the thin filaments and contains only the shafts of myosin molecules. The darker peripheral portions of the A bands are regions of overlap between the thick and thin filaments and contain the heads of the myosin molecules. The interaction between the myosin heads of the thick filaments and the free ends of the thin filaments causes muscle contraction (Fig 10-2).



2. Sarcoplasmic reticulum is the SER of striated muscle cells, specialized to sequester calcium ions. In skeletal muscle, it consists of an anastomosing complex of membrane-limited tubules and cisternae that ensheathe each myofibril. At each A-I band junction, a tubular invagination of the sarcolemma termed a transverse tubule, or T tubule, penetrates the muscle fiber and comes to lie close to the surface of the myofibrils. On each side of the T tubule lies an expansion of the sarcoplasmic reticulum termed a terminal cisterna, A complex of 2 terminal cisternae and an intervening T tubule constitutes a triad, Triads are important in initiating muscle contraction (II.I>).
3. Types of skeletal muscle fibers. Three basic skeletal muscle fiber types differ in myoglobin content, number of mitochondria, and speed of contraction. In humans, most skeletal mus cles are composed of a mixture of these fiber types. a. Red fibers contain more myoglobin and mitochondria and are capable of sustained contraction. Their contraction in response to nervous stimulation is slow and steady, resulting in their designation as slow fibers. They predominate in postural muscles and in the limbs. b, White fibers contain less myoglobin and fewer mitochondria. They react quickly, with brief, forceful contractions, but cannot sustain contraction for long periods. They are thus termed fast fibers, They predominate in the extraocular muscles. c, Intermediate fibers have structural and functional characteristics between those of red and white fibers but are considered a subclass of the latter. They are found dispersed among the red and white fibers in muscles where either type predominates.

C. Motor End-Plates: A motor end-plate, or myoneuraljunction, is a collection of specialized synapses of the terminal boutons of a motor neuron with the sarcolemma of a skeletal muscle fiber (Fig 10-3). It transmits nerve impulses to muscle cells, initiating contraction. Each myoneural junction has 3 major components:


1, The presynaptic (neural) component is the terminal bouton. Although extensions of Schwann cell cytoplasm cover the bouton, the myelin sheath ends before reaching it. The bouton contains mitochondria and acetylcholine-filled synaptic vesicles. The part of the bouton's plasma membrane directly facing the muscle fiber is the presynaptic membrane.
2. The synaptic cleft lies between the presynaptic membrane and the opposing postsynaptic membrane and contains a continuation of the muscle fiber's basal lamina, It also contains acetylcholinesterase , which breaks down the neurotransmitter so that when neural stimulation ends, contraction ends. The primary synaptic cleft lies directly beneath the presynaptic membrane and communicates directly with a series of secondary synaptic clefts created by infoldings of the postsynaptic membrane.
3. The postsynaptic (muscular) component includes the sarcolemma (postsynaptic mem brane) and the sarcoplasm directly under the synapse. The postsynaptic membrane contains receptors for acetylcholine and is thrown into numerous junctional folds. The sarcoplasm beneath the folds contains nuclei, mitochondria, ribosomes, and glycogen.

D. Mechanism of Contraction: According to the sliding-filament hypothesis, skeletal muscle contraction is initiated by and includes the following chain of events:


1. The nerve impulse is carried along the axon of the motor neuron and causes
2. depolarization of the presynaptic membrane (Na+ influx), which causes
3. fusion of the synaptic vesicles with the presynaptic membrane and exocytosis of acetylcholine into the synaptic cleft.
4. Acetylcholine crosses the synaptic cleft and binds to receptors in the postsynaptlc mem- brane, causing
5. depolarization of the sarcolemma (influx of Na+), causing
6. depolarization of the T tubules (sarcolemmal invaginations), causing
7. depolarization of the terminal cisternae, causing
8. depolarization of the rest of the sarcoplasmic reticulum, causing
9. release of sequestered Ca2+ from the sarcoplasmic reticulum into the sarcoplasm surrounding the myofibrils. 10. Ca2t. binds to the TnCs of the troponin complexes, causing
11. a conformational change of each troponin complex, causing
12. the TnIs of the troponin complexes to move away from the myosin head-binding sites on the actin filaments, allowing the
13. myosin heads to bind to actin, causing
14. activation of the ATPase in the myosin heads, causing
15. the production of energy and ADP from ATP (II.F) and movement of the myosin heads, which
16. pull the actin filaments toward the center of the sarcomere, resulting in
17. simultaneous shortening of the sarcomeres by shortening of the I bands (A bands do not narrow), resulting in
18. shortening of the myofibrils, resulting in
19. shortening of the entire muscle fiber.

E. Relaxation: When neural stimulation ends, all the membranes repolarize, allowing the sar coplasmic reticulum to sequester Ca2t from the sarcoplasm by active transport. This removes Ca" from the TnC and returns the TnI to a position in which it inhibits binding of the myosin head to the actin filament.

F. Energy Production: Muscles use glucose (from stored glycogen and from the blood) and fatty acids (from the blood) to form the ATP and phosphocreatine that provide chemical energy for contraction. When ATP is not available, actin-myosin binding become stabilized, accounting for rigor mortis, the muscular rigidity that occurs shortly after death.

G. Organization of the Skeletal Muscles: Named muscles leg, biceps brachii) are bundles of muscle fascicles surrounded by a sheath of dense connective tissue termed the epimysium. Each fascicle is a bundle of muscle fibers surrounded by a dense connective tissue sheath called the perimysium, which consists of septumlike inward extensions of epimysium. Each muscle fiber is a bundle of myofibrils surrounded by a delicate connective tissue sheath termed the endo mysium, which consists of a basal lamina and a loose mesh of reticular fibers. Each myofibril is a bundle of myofilaments surrounded by an investment of sarcoplasmic reticulum, with a triad at both A-I junctions of each sarcomere. The connective tissue investments are continuous with one another.

H, Muscle-Tendon Junctions: The attachment of muscle to tendon must be secure to prevent the muscle from tearing away during contraction. The tendon's collagen fibers blend with the epi mysium and penetrate the muscle along with the perimysium. Near the junction with the tendon, the ends of the muscle cells taper and exhibit many infoldings of their sarcolemmas. Collagen and reticular fibers enter the infoldings, penetrate the basal lamina, and attach directly to the outer surface of the sarcolemma. The attachment of actin filaments to the inner surface of the sar colemma helps stabilize the association between the collagen fibers and the muscle cell.

I. Pattern of Innervation: Each motor neuron has a single axon that may terminate on a single muscle fiber or undergo terminal branching (arborization) and terminate on multiple muscle fibers. A motor neuron and all the muscle fibers it innervates (one to > 100) is termed a motor unit. Muscles responsible for delicate movements leg, extraocular muscles) are composed of many small motor units; those responsible for coarser movements leg, gluteus maximus) are composed of a few large motor units.

III. CARDIAC MUSCLE

A. Histogenesis: Cardiac muscle arises as parallel chains of elongated splanchnic mesenchymal cells in the walls of the embryonic heart tube. Cells in each chain develop specialized junctions between them and often branch and bind to cells in nearby chains. As development continues, the cells accumulate myofilaments in their sarcoplasm. The branched network of myobiasts forms interwoven bundles of muscle fibers, but cardiac myoblasts do not fuse.

B. Cardiac Muscle Cells: Cardiac muscle fibers are long, branched cells with one or 2 ovoid central nuclei. The sarcoplasm near the nuclear poles contains many mitochondria and glycogen granules and some lipofuscin pigment. Mitochondria lie in chains between the myofilaments. The arrangement of myofilaments yields striations like those of skeletal muscle.


1. Sarcoplasmic reticnlum and T tubule system. The sarcoplasmic reticulum in cardiac muscle fibers is less organized than that of skeletal muscle and does not subdivide myofila ments into discrete myofibrillar bundles. Cardiac T tubules occur at the Z line instead of the A-I junction. In most cells, cardiac T tubules associate with a single expanded cisterna of the sarcoplasmic reticulum; thus, cardiac muscle contains dyads instead of triads.
2. Intercalated disks. These unique histologic features of cardiac muscle appear as dark transverse lines between the muscle fibers and represent specialized junctional complexes. With the EM, intercalated disks exhibit 3 major components arranged in a stepwise fashion. a. The fascia adherens, similar to a zonula adherens (see Chapter 4), is a half Z line found in the vertical (transverse) portion of the step. Its cr-actinin anchors the thin tilaments of the terminal sarcomeres. b. The macula adherens (desmosome; see Chapter 4) is the second component of trans verse portion of the junction. It prevents detachment of the cardiac muscle fibers from one another during contraction. c. The gap junctions (see Chapter 4) of intercalated disks form the horizontal (lateral) portion of the step. They provide electrotonic coupling between adjacent cardiac muscle fibers and pass the stimulus for contraction from cell to cell.
3. Types of cardiac muscle fibers a. Atrial cardiac muscle fibers are small and have fewer T tubules than ventricular cells. They contain many small membrane-limited granules that contain a precursor of atrial natriuretic factor, a hormone secreted in response to increased blood volume that opposes the action of aldosterone (see Chapters 19 and 21) and acts on the kidneys to cause sodium and water loss. b. Ventricular cardiac muscle fibers are larger cells with more T tubules and no granules.

C. Organization of Cardiac Muscle: Because of the abundant capillaries in the endomysium, cardiac muscle fibers appear more loosely arranged in histologic section than those of skeletal muscle. The whorled arrangement of cardiac muscle fibers in the wall of the heart accounts for the ability of the myocardium to "wring out" blood in the heart chambers (see Chapter II).

D. Mechanism of Contraction: Although the arrangement of the sarcoplasmic reticulum and T tubule complex of cardiac muscle fibers differs from that of skeletal muscle, the composition and arrangement of myofilaments are almost identical. Thus, at the cellular level, skeletal and cardiac muscle contractions are essentially the same.

E. Initiation of Cardiac Muscle Contraction: Unlike skeletal muscle fibers, which rarely con tract without direct motor innervation, cardiac muscle fibers contract spontaneously with an intrinsic rhythm. The heart receives autonomic innervation through axons that terminate near, but never form synapses with, cardiac muscle cells. The autonomic stimulus cannot initiate contraction but can speed up or slow down the intrinsic beat. The initiating stimulus for contraction is normally provided by a collection of specialized cardiac muscle cells called the sinoatrial node; it is delivered by other specialized cells, called Purkinje fibers, to the other cardiac muscle cells. The stimulus is passed between adjacent cells through the gap junctions of the intercalated disks. The gap junctions establish an ionic continuity among cardiac muscle fibers that allows them to work together as a functional syncytium. For more details, see Chapter 11.

IV. SMOOTH MUSCLE

A. Histogenesis: Most smooth muscle cells differentiate from mesenchymal cells of mesoder mal origin in the walls of developing hollow organs of cardiovascular, digestive, urinary, and reproductive systems. During differentiation, the cells elongate and accumulate myofilaments. Smooth muscles of the iris arise from ectoderm.

B. Smooth Muscle Cells: Mature smooth muscle fibers are spindle-shaped cells with a single central ovoid nucleus. The sarcoplasm at the nuclear poles contain abundant mitochondria, some RER, and a large Golgi complex. Each fiber produces its own basal lamina, consisting of proteoglycan-rich material and type III collagen fibers.


1. Myofilaments a. Thin filaments. The actin filaments of smooth muscle are like those of skeletal and cardiac muscle. They are always present in the cytoplasm and are anchored by alpha-actinin dense bodies associated with the plasma membrane. b. Thick filaments. The myosin filaments of smooth muscle are less stable than those in striated muscle cells; they are not always present in the cytoplasm but seem to form in response to a contractile stimulus (IV.D). Unlike the thick filaments in striated muscle cells (II.B. I.b), those in smooth muscle have heads along most of their length and bare areas at the ends of the filaments. c. Organization of the myofilaments. The filaments run mostly parallel to the long axis of smooth muscle fibers, but they overlap much more than those of striated muscle, accounting for the absence of cross striations. The greater overlap of thick and thin filaments results from the unique organization of the thick filaments (see above) and permits greater contraction. The ratio of thin to thick filaments in smooth muscle is about 12:1, and the arrangement of the filaments is less regular and crystalline than in striated muscle.
2. Sarcoplasmic reticulum.Smooth muscle cells contain a poorly organized sarcoplasmic reticulum that participates in the sequestration and release of Ca2f but does not divide the myofilaments into myofibrillar bundles. Abundant surface-associated membrane-limited ves icles termed caveolae appear to aid in Ca2+ uptake and release. The small size and slow contraction of these fibers make an elaborate stimulus-conducting system unnecessary; these fibers have no T tubules, dyads, or triads.
3. Types of smooth muscle fibers. Although smooth muscle cells exhibit similar morphology in histologic section, they can be classified according to developmental, biochemical, and functional differences. a. Visceral smooth muscle derives from splanchnopleural mesenchyme and is found in the walls of the hollow thoracic, abdominal, and pelvic organs of the respiratory, digestive, urinary, and reprc;ductive systems. In addition to thick myosin and thin actin filaments, its sarcolemma-associated dense bodies are linked by desmin-containing intermediate filaments. Because of their poor nerve supply, the cells transmit contractile stimuli to one another through their abundant gap junctions, acting as a functional syncytium. Contraction is slow and in waves. Visceral smooth muscle is classed as unitary smooth muscle. b. Vascular smooth muscle differentiates in situ from mesenchyme around developing blood vessels. Its cells have intermediate filaments containing vimentin as well as des min. It has the same functional features as visceral smooth muscle and is also classed as unitary smooth muscle, although its waves of contraction are not sustained and are localized. c. Smooth muscle of the iris. The sphincter and dilator pupillae muscles are unique. Their cells derive from ectoderm and have a rich nerve supply. They are classed as multiunit smooth muscle because the cells can contract individually; they are capable of precise and graded contractions.

C. Organization of Smooth Muscle: Unlike striated-muscle fibers, which abut end-to-end, smooth muscle fibers overlap to various degrees and attach to one another by fusing their endomysial sheaths. The sheaths are interrupted by many gap junctions, which transmit the ionic currents that initiate contraction. Smooth muscle fibers form fascicles that vary in size but are usually smaller than those in striated muscle. The fascicles, each surrounded by a meager perimysium, are often organized in layers separated by the thicker epimysial connective tissue. Fibers in adjacent layers often lie perpendicular to one another.

D. Mechanism of Contraction: The mechanism of smooth muscle contraction is a modification of the sliding-filament mechanism. At the beginning of the contraction, the myosin filaments appear and the actin filaments are pulled toward and between them. Continued contraction involves forming more myosin filaments and further sliding of the actin filaments. The sliding actin filaments pull the attached dense bodies closer together, shortening the cell. Unlike striated muscle fibers, individual smooth muscle fibers may undergo partial peristaltic, or wavelike, contractions. During relaxation, the myosin filaments decrease in number, disintegrating into soluble cytoplasmic components.

E. Initiation of Smooth Muscle Contraction: Like cardiac muscle fibers, smooth muscle fibers are capable of spontaneous contraction that may be modified by autonomic innervation. Motor end-plates are not present. Neurotransmitters diffuse from terminal expansions of the nerve endings between smooth muscle cells to the sarcolemma. Both sympathetic (adrenergic) and parasympathetic (cholinergic) endings are present and exert antagonistic (reciprocal) effects. In some organs, contractile activity is enhanced by cholinergic nerves and decreased by adrenergic nerves, whereas in others the opposite occurs.

V. RESPONSE OF MUSCLE TO INJURY

The response of muscle to injury depends on the muscle type. The wound closure mechanism always involves the proliferation of fibroblasts in the perimyseal and epimyseal connective tissue and the synthesis of connective tissue matrix materials.

A. Skeletal Muscle: Small, mononucleatcd satellite cells are scattered in adult skeletal muscles within the basal lamina of the mature fibers. While mature skeletal muscle fibers are incapable of mitosis, the normally quiescent satellite cells can divide following muscle injury, differentiate into myoblasts, and fuse to form new skeletal muscle fibers.

B. Cardiac Muscle: Cardiac muscle has little regenerative ability beyond early childhood. Le- sions of the adult heart are repaired by replacement with connective tissue scars.

C. Smooth Muscle: Smooth muscle contains a population of relatively undifferentiated mono nucleated smooth muscle precursors that proliferate and differentiate into new smooth muscle fibers in response to injury. The same mechanism appears to be involved in adding new muscle to the myometrium as the uterus enlarges during pregnancy to accommodate the growing fetus.

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