Muscle Tissue

Department Of General Histology

Introduction• Muscle tissue is composed of cells differentiated for optimal use of the

universal cell property termed contractility. Microfilaments and associated proteins together generate the forces necessary for cellular contraction, which drives movement within certain organs and the body as a whole. Nearly all muscle cells are of mesodermal origin and they differentiate mainly by a gradual process of cell lengthening with simultaneous synthesis of myofibrillar proteins.

• Three types of muscle tissue can be distinguished on the basis of morphologic and functional characteristics (Figure 10–1) and the structure of each type is adapted to its physiologic role. Skeletal muscle is composed of bundles of very long, cylindrical, multinucleated cells that show cross-striations. Their contraction is quick, forceful, and usually under voluntary control. It is caused by the interaction of thin actin filaments and thick myosin filaments whose molecular configuration allows them to slide upon one another. The forces necessary for sliding are generated by weak interactions in the bridges between actin and myosin. Cardiac muscle also has cross-striations and is composed of elongated, branched individual cells that lie parallel to each other. At sites of end-to-end contact are the intercalated disks, structures found only in cardiac muscle. Contraction of cardiac muscle is involuntary, vigorous, and rhythmic. Smooth muscle consists of collections of fusiform cells that do not show striations. Their contraction process is slow and not subject to voluntary control.

Types of muscle

Skeletal muscle is composed of large, elongated, multinucleated fibers that show strong, quick, voluntary contractions.

Cardiac muscle is composed of irregular branched cells bound together longitudinally by intercalated disks and shows strong, involuntary contractions.

Smooth muscle is composed of grouped, fusiform cells with weak, involuntary contractions. The density of intercellular packing seen reflects the small amount of extracellular connective tissue present.

Development of skeletal muscle

Organization of skeletal muscle (a): An entire skeletal muscle is

enclosed within a dense connective tissue layer called the epimysium continuous with the tendon binding it to bone.

(b): Each fascicle of muscle fibers is wrapped in another connective tissue layer called the perimysium.

(c): Individual muscle fibers (elongated multinuclear cells) is surrounded by a very delicate layer called the endomysium, which includes an external lamina produced by the muscle fiber (and enclosing the satellite cells) and ECM produced by fibroblasts.

Skeletal muscle

Micrograph shows a cross section of striated muscle demonstrating connective tissue and cell nuclei. The endomysium around individual muscle fibers is indicated by arrowheads. At left is a portion of the epimysium. All three of these tissues contain collagen types I and III (reticulin).

Adjacent section immunohistochemically stained for laminin, which specifically stains the external lamina part of the endomysium produced by the muscle fibers themselves.

Capillaries of skeletal muscle

The blood vessels were injected with 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.

Myotendinous junction

Tendons develop together with skeletal muscles and join muscles to the periosteum of bones. The collagen fibers of tendons are continuous with those in the connective tissue layers in the muscle, forming a strong unit that allows muscle contraction to move the skeleton. The longitudinal section shows part of a tendon (T) inserted into the endomysium and perimysium of a muscle.

Striated skeletal muscle in longitudinal section

Parts of three muscle fibers separated by very small amounts of endomysium. One fibroblast nucleus (F) is shown. Muscle nuclei (N) are found against the sarcolemma. Along each fiber thousands of dark-staining A bands alternate with lighter I bands.

At higher magnification, each fiber can be seen to have three or four myofibrils, with their striations slightly out-of-alignment with one another. Myofibrils are cylindrical bundles of thick and thin myofilaments which fill most of each muscle fiber. The middle of each I band can be seen to have a darker Z line (or disk). X500. Giemsa.

TEM showing the more electron-dense A bands bisected by a narrow, less electron-dense region called the H zone and in the I bands the presence of sarcoplasm with mitochondria (M), glycogen granules, and small cisternae of SER around the Z line.

Structure of a myofibril: a series of sarcomeres

(a): Diagram indicates that each muscle fiber contains several parallel bundles called myofibrils. (b): Each myofibril consists of a long series of sarcomeres which contain thick and thin filaments and are separated from one another by Z discs. (c): Thin filaments are actin filaments with one end bound to -actinin, the major protein of the Z disc. Thick filaments are bundles of myosin, which span the entire A band and are bound to proteins of the M line and to the Z disc across the I bands by a very large protein called titin, which has spring-like domains. (d): The molecular organization of the sarcomeres has bands of greater and lesser protein density, resulting in staining differences that produce the dark and light-staining bands seen by light microscopy and TEM. (e): TEM cross-sections through different regions of the sarcomere, as shown here, were useful in determining the relationships between thin and thick myofilaments and other proteins, as shown in part b of this figure. Thin and thick filaments are arranged so that each myosin bundle contacts six actin filaments.

Molecules composing thin and thick filaments

Each thin filament is composed of F-actin, tropomyosin, and troponin complexes.

Each thick filament consists of many myosin heavy chain molecules bundled together along their rod-like tails, with their heads exposed and directed toward neighboring thin filaments.

Besides interacting with the neighboring thin filaments, thick myofilament bundles are held in place by less well-characterized myosin-binding proteins within the M line.

Transverse tubule system

TEM shows portions of two fibers in cross-section and the intercellular space, and includes several transverse or T tubules cut lengthwise (arrows).

TEM of a longitudinal section of skeletal muscle shows T tubules cut transversely (arrowheads) near the A-I interface, the most common location of T tubules in muscles of primates. Between the three myofibrils seen shown here is sarcoplasm containing mitochondria (M) and sarcoplasmic reticulum. Cisternae of this reticulum usually lie on each side of the transverse tubules, forming the triad of structures responsible for the cyclic release of Ca2+ from the cisternae and its sequestration again which occurs during muscle contraction and relaxation. The association between SR cisternae and T tubules is shown diagrammatically in the next figure.

Events of muscle contraction.

Sliding filaments and sarcomere shortening in contraction

In their relaxed state the sarcomere, I band and H zone are at their expanded length. The spring-like action of titin molecules, which span the I band, help pull thin and thick filaments past one another in relaxed muscle.

The Z discs at the sarcomere boundaries are drawn closer together during contraction as they move toward the ends of thick filaments in the A band. Titin molecules are compressed during contraction.

At maximal contraction, the H zone and I bands narrow and may disappear altogether.

The neuromuscular junction (NMJ).

Silver staining can reveal the nerve bundle (NB), the terminal axonal twigs, and the motor end plates (MEP) on striated muscle fibers (S).

A SEM shows the branching ends of a motor axon, each covered by an extension of the last Schwann cell and expanded terminally as a motor end plate embedded in a groove in the external lamina of the muscle fiber.

Diagram indicating key features of a typical neuromuscular junction: synaptic vesicles of acetylcholine (ACh), a synaptic cleft, and a postsynaptic membrane. This membrane, the sarcolemma, is highly folded to increase the number of Ach receptors at the NMJ. Receptor binding initiates muscle fiber depolarization, which is carried to the deeper myofibrils by the T tubules.

Sensory receptors associated with skeletal muscle

Diagram shows both a muscle spindle and a tendon organ. Muscle spindles have afferent sensory and efferent motor nerve fibers associated with the intrafusal fibers, which are modified muscle fibers. The size of the spindle is exaggerated relative to the extrafusal fibers to show better the nuclei in the intrafusal fibers.

TEM cross-section near the end of a muscle spindle shows the capsule (C), sensory myelinated axons (MA), and the intrafusal muscle fibers (MF). These thin fibers differ from the ordinary skeletal muscle fibers in having essentially no myofibrils. Their many nuclei can either be closely aligned (nuclear chain fibers) or piled in a central dilatation (nuclear bag fibers). Satellite cells (SC) are also present within the external lamina of intrafusal fibers. Muscle spindles detect contraction of neighboring (extrafusal) muscle fibers during body movement and participate in the nervous control of body posture and the coordinate action of opposing muscles. The tendon organ collects information about the degree of tension among tendons and relays this data to the CNS, where the information is processed with that from muscle spindles to protect myotendinous junctions and help coordinate fine muscular contractions.

Skeletal muscle fiber types

Cardiac muscle

Cardiac muscle fibersLongitudinal sections of cardiac muscle at the light microscope level show nuclei (N) in the center of the muscle fibers and widely spaced intercalated discs (I) that cross the fibers. The occasional intercalated discs should not be confused with the repetitive, much more closely spaced striations (S), which are similar to those of skeletal muscle but less well-organized. Nuclei of fibroblasts in the endomysium are also present.

TEM of an intercalated disc (arrows) shows a steplike structure representing the short interdigitating processes of the adjacent muscle cells. Transverse regions of the disc have many desmosomes (D) and adherent junctions called fascia adherentes (F), somewhat similar to the macula adherentes of epithelial cells. Fascia adherentes serve as anchoring sites for actin filaments of the terminal sarcomeres. Less electron-dense regions of the disc have abundant gap junctions. The sarcoplasm has numerous mitochondria (M) and myofibrillar structures similar to those of skeletal muscle but slightly less organized.

Cardiac muscle ultrastructure

TEM of cardiac muscle shows an abundance of mitochondria (M) and rather sparse sarcoplasmic reticulum (SR) in the areas between myofibrils. T tubules are less well-organized and are usually associated with one expanded terminal cisterna of SR, forming dyads (D) rather than the triads of skeletal muscle. Functionally these structures are similar in these two muscle types.

Muscle cell from the cardiac atrium shows the presence of membrane-bound granules aggregated at the nuclear poles. These granules are most abundant in muscle cells of the right atrium (~600 per cell), but smaller quantities are also found in the left atrium and the ventricles. The atrial granules contain the precursor of a polypeptide hormone, atrial natriuretic factor (ANF). ANF targets cells of the kidneys to bring about sodium and water loss (natriuresis and diuresis). This hormone thus opposes the actions of aldosterone and antidiuretic hormone, whose effects on kidneys result in sodium and water conservation.

Smooth muscle

In a cross-section of smooth muscle in the wall of the small intestine, cells of the inner circular (IC) layer are cut lengthwise and cells of the outer longitudinal layer (OL) cross 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.

Section of smooth muscle in bladder, shows fibers in cross-section (XS) and longitudinal section (LS) with the same fascicle. There is much collagen in the branching perimysium (P), but very little evidence of endomysium is apparent. X140. Mallory trichrome.

Section stained only for reticulin reveals a thin endomysium around each fiber, with more reticulin in the connective tissue of small arteries (A). Reticulin fibers in the basal laminae of smooth muscle cells help hold the cells together as a functional unit during the slow, rhythmic contractions of this tissue.

Smooth muscle ultrastructure

TEM of a transverse section of smooth muscle showing six or seven cells sectioned at various points along their lengths, yielding profiles of various diameters with only the largest containing a nucleus. Thick and thin filaments are not organized into myofibril bundles and there are few mitochondria (M). There is evidence of a sparse external lamina around each cell and reticular fibers are abundant in the ECM. A small unmyelinated nerve (N) is also seen between the cells.

Longitudinal section showing several dense bodies in the cytoplasm (arrows) and at the cell membrane. Thin filaments and intermediate filaments both attach to the dense bodies. In the cytoplasm near the nucleus (N) are mitochondria, glycogen particles, and Golgi complexes. In the area shown at the lower right, the cell membrane shows invaginations called caveoli (C) (L. caveoli, little cavities), which in many cells are indicative of endocytosis, but in smooth muscle cells, where they are particularly numerous, may also function as the T tubules of skeletal muscle fibers and regulate release of Ca2+ from sarcoplasmic reticulum.

Smooth muscle contractionThe diagram shows thin filaments attach to dense bodies located in the cell membrane and deep in the cytoplasm. Dense bodies contain -actinin for thin filament attachment. Dense bodies at the membrane are also attachment sites for intermediate filaments and for adhesive junctions between cells. This arrangement of both the cytoskeleton and contractile apparatus allows the multicellular tissue to contract as a unit, providing better efficiency and force.

Contraction decreases the length of the cell, deforming the nucleus and promoting contraction of the whole muscle. The micrograph shows a region of contracted tissue in the wall of a urinary bladder. The long nuclei of individual fibers assume a cork-screw shape when the fibers contract, reflecting the reduced cell length at this time.

Regeneration of Muscle Tissue• The three types of adult muscle have different potentials for regeneration

after injury.• In skeletal muscle, although the nuclei are incapable of undergoing mitosis,

the tissue can undergo limited regeneration. The source of regenerating cells is the sparse population of mesenchymal satellite cells that lies within the external lamina of each mature muscle fiber. Satellite cells are inactive, reserve myoblasts that persist after muscle differentiation. After injury or certain other stimuli, 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 their parent fibers to increase muscle mass beyond that occurring by cell hypertrophy. The regenerative capacity of skeletal muscle is limited, however, after major muscle trauma or degeneration.

• Cardiac muscle lacks satellite cells and has virtually no regenerative capacity beyond early childhood. Defects or damage (eg, infarcts) in heart muscle are generally replaced by fibroblast proliferation and growth of connective tissue, forming myocardial scars. Smooth muscle, composed of simpler, mononucleated cells, is capable of 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.

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