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Muscle Tissue

Page history last edited by John Aho 12 years, 3 months ago

Barbara M. Vertel, Ph.D.

Histology/Physiology 2005

 

Muscle Tissue

 

Reading: Junqueira (2003) Basic Histology, 10th ed. Ch. 10

Gartner & Hiatt (2001). Color Textbook of Histology, 2nd Ed. Ch. 8.

Also refer to Alberts et al. (2002) pp. 961-965; Lodish et al. (2004) pp. 226-7, 811


I. General Introduction

 

Muscle tissue, one of the four tissue types, is specialized for contraction and body movement. Muscle cells have either a striated or a non-striated appearance, depending upon the arrangement of contractile elements within the cells. Control of contraction is either voluntary or involuntary, based on the type of muscle. Muscle is classified into three main types, skeletal (striated, voluntary), cardiac (striated, involuntary), and smooth (non-striated, involuntary), characterized by structure and function (Figs. 1-6).

 

II. Skeletal Muscle

 

Skeletal muscle cells, also called muscle cell fibers, are specialized for rapid, forceful, vountary contractions. They form the muscles of the musculoskeletal system. In addition, they form some muscles that do not move bones, such as the diaphragm, extraocular muscles, and muscles of facial expression. Skeletal muscle tissue is also found in parts of the digestive and respiratory systems.

Skeletal muscle cells have prominent cross-striations in the cytoplasm that are visible by both light and electron microscopy. The cells are large and do not branch. Typical dimensions are 10-100 µm in diameter and 1-40 mm in length. Each cell is multinucleated, with peripherally located nuclei. Thus, the skeletal muscle cell is a syncytium (Fig. 7, 8) many nuclei in a common cytoplasm) that arises during embryonic development by the fusion of mononucleated myoblasts (Fig. 11).

  • A. Additional Features of Skeletal Muscle Cells
    • 1. Contractile elements fill the cytoplasm (sarcoplasm). They are comprised of thin, actin-containing myofilaments that also contain associated troponin and tropomyosin and thick, myosin myofilaments arranged in a highly ordered manner, forming sarcomeres and myofibrils. Myofilaments are assembled to form sarcomeres, which are aligned in series to form myofibrils. Many myofibrils are contained within the cytoplasm of each muscle cell, or myofiber. The precise array of myofilaments within the myofibrils and the alignment of myofibrils with sarcomeres in register gives the muscle cell its striated appearance, with dark "A" (anisotropic) bands, light "I" (isotropic) bands and thin, dark "Z" lines (Fig. 12-16). The sarcomere, which extends from one Z line to the next Z line, is the repeating unit of the band pattern, and is the functional unit of contraction in striated muscle (Fig. 17, 19).

      Dark A-bands (anisotropic) and light I-bands (isotropic) alternate. The A-bands are birefringent in polarized light (anisotropic). A-bands contain both thick and thin filaments. I-bands have no effect on polarized light; they are isotropic. I-bands contain only thin filaments. The dark A bands have a lighter central zone called the H-band. H-bands contain only thick filaments. A thin M-line bisects the H band (and A band). The dark, thin Z-line bisects the I band.

      The Sliding Filament Model explains the mechanism of contraction involving myofilaments (Fig. 20-24, refer to MCB Muscle notes/Dr. Neet for details). Thin filaments are anchored at Z-lines, the ends of the sarcomere. Thick filaments are present in the center of the sarcomere. Thick and thin filaments overlap at the ends of the A-band. Each thick filament is surrounded by 6 thin filaments. Transient interactions between myosin cross bridges and actin thin filaments are important for the repeated cycles of contraction. Activation of the contractile mechanism causes thin filaments and thick filaments to slide past each other, causing the Z lines to come closer together and the sarcomere to shorten (Fig. 23, 24).

       

    • 2. Contractile elements in the sarcomere are organized within a structural framework or scaffold involving 15-20 other proteins (Fig. 25-32). Several are discussed here. These include the extremely large proteins, titin (MW- 2,700,000, 9% muscle protein), and nebulin (MW - 700,000, 3% muscle protein) that are involved in positioning the thick and thin filaments, respectively. Titin forms a network of filaments running parallel to the thick and thin filaments in the sarcomere and appears to link the myosin thick filaments with the Z-disc. The titin filaments are thought to be anchored along the surface of the thick filaments with a segment with elastic properties that runs between the end of the thick filament and the Z-disc. These filaments keep the myosin thick filaments centered between the Z-lines of the sarcomere. Nebulin extends from each side of the Z-disc along the thin filaments as non-elastic filaments as long as the thin filaments. This relationship may suggest a role for nebulin in regulating the lengths of the thin filaments. Nebulin is present in skeletal, but not cardiac, muscle. Cap Z and tropomodulin regulate the length of the actin thin filaments. Myomesin and M protein stabilize myosin thick filaments in the sarcomere by interactions at the M line that maintains their parallel configuration in a region where thin filaments are absent. Actin thin filaments are stabilized at the Z line by α-actinin, which anchors actin filaments at their (+) ends, and by the intermediate filament protein, desmin. Desmin also provides a framework of intrafibrillar and interfibrillar structures.

       

    • 3. Each skeletal muscle cell contains many nuclei, located in the periphery of the cell and flattened against the plasma membrane (sarcolemma) by the abundant myofibrils (Fig. 8, 9, 12). Non-fibrillar cytoplasm is mostly restricted to perinuclear regions. The Golgi apparatus is located in this region, along with a small amount of rough endoplasmic reticulum, free ribosomes, and lysosomes. Mitochondria (sarcosomes), lipid droplets and glycogen particles are found in both perinuclear and interfibrillar areas.

       

    • 4. Membrane specializations of skeletal myofibers include the sarcoplasmic reticulum (SR), which is a specialization of the endoplasmic reticulum, and transverse tubules (T-tubules), which are specializations of the sarcolemma (Figs. 34-41). The SR is a prominent intracellular feature. The SR surrounds myofibrils and is in close structural association with the T-tubules. The T-tubules are formed by deep invaginations of the sarcolemma. Together, the terminal cisternae of the sarcoplasmic reticulum and the T-tubule form the triad structure, located at the level of the A-I band in mammalian skeletal muscle (thus, two triads associated with each sarcomere). After nervous stimulation at the neuromuscular junction (see below) depolarization is carried along the membrane of the T-tubule, which is a specialized region of the muscle cell plasma membrane. At the triad, the T-tubule signals the SR to release its store of intracellular Ca++. When Ca++ is released into the sarcoplasm, myofibrils enter the contraction cycle. Contraction ends when Ca++ is removed from the sarcoplasm and re-sequestered into the SR.

      At triads, spaced densities or "feet" are observed in electron micrographs extending between SR and T-tubule membranes (Fig. 40). These structures are assemblies of membrane and associated proteins that are organized to respond to changes in T-tubule membrane potential and stimulate the release of calcium from the SR. The calcium release channel, ryanodine receptor is assembled into oligomers within the membrane of the terminal cisterna of the SR that correspond to the foot-like structures and are involved in signal transduction leading to release of Ca++ from stores within the SR lumen.

      The SR also acts to remove C++ from the sarcoplasm (cytosol) and thereby stop contraction. The membrane of SR contains an abundant Ca++ transport protein, Ca++ATPase, which hydrolyses ATP and actively transports Ca++ against its concentration gradient into the lumen of the SR. Ca++ in the sarcoplasm is approx. 10-7 during relaxation and 10-5 M during contraction. It is stored in the SR at a concentration of approx. 10-3M. A calcium binding protein in the SR, calsequestrin, binds and aids in concentrating Ca++.

  • B. The Neuromuscular Junction (Fig. 42-50)
    • Nervous stimulation of a skeletal myofiber occurs at the neuromuscular junction, a specialized structure found at the site where the myofiber and axon of the neuron meet (Figs. 42-50). At the neuromuscular junction, the sarcolemma of the skeletal myofiber invaginates to form the primary synaptic cleft, a shallow trough in which the axon terminal lies. The sarcolemma invaginates further into numerous, deep secondary synaptic clefts, or junctional folds. This specialization of the sarcolemma at the neuromuscular junction serves to greatly increase the surface area at the site where the axon and myofiber are in close contact. The neurotransmitter acetylcholine is released from the axon terminal and binds to specific acetylcholine receptors in the junctional sarcolemma, resulting in depolarization of the muscle cell membrane, which triggers contraction of the myofiber. Acetylcholinesterase, present in the external lamina of the synaptic clefts, degrades the acetylcholine on site and thereby prevents multiple responses and permits reestablishment of the resting potential.
  • C. Red, White and Intermediate Skeletal Muscle Fibers (Fig. 51-52)
    • Skeletal muscle fibers are heterogeneous. On a gross level, this is reflected in differences in the color of skeletal muscles. Red myofibers are highly aerobic cells and are most abundant in muscles that function in slow, sustained contraction. White myofibers have a high capacity for anaerobic metabolism (high levels of glycogen and glycolytic enzymes) and predominate in muscles that function in rapid, sporadic, intense contraction-fast twitch. Intermediate myofibers exhibit characteristics intermediate between red and white fibers, but they superficially resemble red fibers and are prevalent in red muscles.
      • 1. Red myofibers predominate in so-called "red" muscles. These myofibers are relatively small in diameter and have an abundance of large mitochondria. These mitochondria contain closely-packed cristae and are concentrated in groups beneath the sarcolemma and in longitudinal rows between myofibrils. Red fibers also have a high content of myoglobin and cytochromes and a rich blood supply.
      • 2. White myofibers predominate in so-called "white" muscles. They are much larger in diameter than red myofibers. Mitochondria in white fibers are smaller and more sparse than in red fibers. They are found primarily in pairs at the Z lines. White myofibers also contain less myoglobin and cytochromes than red fibers and have a relatively poor blood supply.
      • 3. Other characteristics of red, white and intermediate myofibers. Neuromuscular junctions also differ among the various skeletal muscle types. The junctions are more complex in white than in red fibers (that is, the number of synaptic vesicles and the number and complexity of junctional folds are the greatest in white fibers and least in red fibers). The distribution of fiber types within a muscle appears to be regulated by innervation. Under certain conditions, a given fiber can change in type from red to white and visa versa.

        Skeletal myofiber types can be distinguished by a number of different histochemical techniques (Fig. 10). Some take advantage of variations in the relative amounts of myoglobin or mitochondrial enzymes. They also differ in the myosin isoform present, and this difference can be observed using antibodies specific for the different myosin isoforms.

  • D. Muscular Dystrophy and Dystrophin (Fig. 54)

    The sarcolemmma and association with the extracellular basal lamina are important for maintaining physical stability of the myofiber under the stress of muscle contraction (Fig. 53-54). The protein dystrophin was discovered in a search for the gene that causes Duchenne musclular dystrophy. It was determined that dystrophin localized near the plasma membrane of muscle fibers. Further studies showed that it anchors the cortical actin network to the extracellular matrix through the interaction of its N-terminus with F-actin, and the interaction of its C-terminus with a transmembrane complex of dystrophin-associated proteins and dystrophin-associated glycoproteins, as diagrammed in Fig. 54. The absence of dystrophin in muscular dystrophy patients causes muscular weakness. In normal muscle, the link between myofibrillar proteins inside the muscle cell and the extracellular basal lamina, mediated by the dystrophin-transmembrane complex, stabilizes these associations and protects the physical integrity of the muscle.

  • E. Muscle as an Organ: Higher Orders of Structure (Figs. 56-59)

    In order for contraction of individual myofibers to result in contraction of the entire muscle body, myofibers are bound together by connective tissue to form a muscle body. Three levels of organization are established by the arrangement of the surrounding connective tissue (Figs. 56-59).

    • 1. Endomysium is connective tissue that surrounds each myofiber. It is a fine network of collagenous and reticular fibers with varying amounts of elastic fibers. Some connective tissue (CT) cells, fine capillaries and nerves are also present. Endomysium blends with the extracellular basal lamina of the myofiber.
    • 2. Perimysium bundles several myofibers into groups called fascicles. It is a loose, irregularly arranged, predominantly collagenous CT. The CT fibers are considerably coarser than in endomysium. Blood vessels and nerves are distributed throughout the muscle body in the perimysium.
    • 3. Epimysium is a dense CT sheath that binds fascicles together to form the muscle body. This is termed deep fascia by gross anatomists. The major blood vessels and nerves penetrate through the epimysium.

 

  • F. Attachment of Skeletal Muscle to Bone: Myotendinous Junctions (Fig. 61-63)

    The skeletal muscles are attached to bone at myotendinous junctions. At the ends of the muscle, the sarcolemma of individual myofibers interdigitates with the collagen and ground substance of the extracellular matrix of tendon. In the electron microscope, actin filaments can be seen extending beyond the last sarcomere into the finger-like projections of the sarcoplasm and attaching at the sarcolemma (Fig. 63).

 

  • G. Muscle Spindles and Golgi Tendon Organs (Fig. 64-67)

    Muscle spindles are stretch receptor organs within skeletal muscles, also called neuromuscular spindles. When muscle is stretched, it normally undergoes reflex contraction, a protective response that prevents the tearing of muscle fibers. The muscle spindles regulate muscle tone via this spinal stretch reflex response.

    Muscle spindles are encapsulated, lymph-filled, fusiform structures that lie parallel to the skeletal myofibers in connective tissue between bundles of myofibers (Fig. 13). They contain two to ten modified muscle fibers, called intrafusal fibers. These myofibers are smaller than more typical skeletal myofibers, known in this context as extrafusal fibers. Each intrafusal fiber has a central, non-striated area in which the nuclei are concentrated. There are two types of intrafusal fibers, nuclear bag fibers and the more numerous nuclear chain fibers. Two types of sensory fiber receptors are associated with intrafusal fibers, annulospiral endings and flower-spray endings. When a muscle is stretched, the sensory fiber receptors are distorted and stimulated, and the relay of this information leads to muscle contraction. For further information, see Gartner & Hiatt pp. 170-172.

    Golgi tendon organs, also called neurotendinous spindles, protect the tendon from the stress resulting from intense periods of muscle contraction by providing an inhibitory feedback to relax the muscle causing contraction of the tendon. Thus, the Golgi tendon organs and muscle spindles have opposing actions and work together to integrate spinal reflex systems. The Golgi tendon organs are composed of collagen fibers of the tendon associated with sensory nerve endings that are stimulated by excessive stretching of the collagen fibers.

  • H. Satellite cells (Fig. 68)

    Even in adult muscle, stem cells, called satellite cells, are present, capable of proliferating after injury to generate new myoblasts, which go on to fuse and form myotubes. These mononucleated cells reside underneath the basal lamina of the myofibers. Thus, skeletal muscle is capable of limited repair, as long as the basal lamina is not disrupted.

 

III. Cardiac Muscle

 

Cardiac muscle cells are found only in the myocardium of the heart and in the walls of the large veins at their junction with the heart. Control of cardiac muscle contraction is involuntary. Like skeletal muscle cells, cardiac myofibers are striated. Thus, striated muscle refers to both skeletal and cardiac muscle. Cardiac myofibers are considerably smaller than skeletal muscle cells and exhibit branching. Typical dimensions are 10-20 µm in diameter and 100-150 µm in length. Only one to two centrally located nuclei are present in each cell. Cardiac myofibers exhibit spontaneous, rhythmic contraction and are joined to each other both structurally and functionally by intercalated disks (Figs. C1-5). Because the gap junctions of the intercalated disks allow for electrotonic coupling between adjacent cells, cardiac muscle functions as a syncytium, but in actuality is not a true syncytium.

  • A. Structural Features of Cardiac Muscle Cells (Figs. C1-13)
    • 1. Myofibrils fill the cytoplasm, although they are less abundant than in skeletal myofibers and more interfibrillar cytoplasm is present. The myofibrils branch and anastamose (i.e., bundles of myofilaments merge with adjacent myofibrils). Sarcomeres are not in register to the same degree as in skeletal myofibers. However, sarcomere banding patterns are recognizable and the arrangement of myofilaments within sarcomere and the myofibril is the same as in skeletal myofibrils. Scaffold proteins are also important, including, among others, the Z-line protein -actinin, M line protein myomesin, the large thick filament-associated protein titin, a thin filament-associated protein like nebulin, called nebulette, and the intermediate filament protein, desmin. In cardiac muscle, desmin is the intermediate filament protein associated with desmosomes of the intercalated disc (see section 5 below), and is critical in providing structural support.
    • 2. One or two ovoid nuclei are found centrally located, between diverging myofibrils.
    • 3. Non-fibrillar subsarcolemmal, perinuclear and interfibrillar cytoplasm contains numerous mitochondria (many more than in skeletal myofibers), a Golgi apparatus, free ribosomes, lysosomes, some rough endoplasmic reticulum, lipid droplets and relatively large deposits of glycogen --more than in skeletal muscle cells (Fig. C9). Mitochondrial, lipid droplets and glycogen particles are especially abundant in interfibrillar areas. In cardiac myofibers, mitochondria may occupy 40% of the cytoplasm. In addition, the mitochondrial cristae are highly elaborated to support aerobic metabolism efficiently.
    • 4. Sarcoplasmic reticulum and T-tubules are prominent in cardiac myofibers, though not as extensive as in skeletal myofibers, and are arranged somewhat differently (Fig. C7-8). Diads, rather than triads are formed between SR and T-tubules and they are present at the Z lines, rather than at the A-I band junctions. The T-tubules are thicker, and SR is less extensive than in skeletal fibers and forms a plexiform pattern with minimal terminal cisternae.
    • 5. Intercalated disks are another prominent feature of cardiac myofibers (Fig. C10-13). These intercellular junctional complexes serve to bind neighboring cardiac myofibers together as well as to provide electrotonic coupling of myofibers. They course between myofibers in a step-wise fashion and thus have both longitudinal and transverse regions. The transverse regions are present at Z lines. Intercalated disks contain several different types of specialized junctions (refer to MCB Cell Adhesion and Intercellular Junctions lecture for further discussion of intercellular junctions): a) Desmosomes provide strong adhesion between cardiac myofibers; b) fascia (zonula) adherens anchor actin filaments of the terminal sarcomeres to the plasma membrane; and c) gap junctions ionically couple cells and provide for the spread of contractile depolarization.
  • B. Associated Connective Tissue

    As with skeletal muscle, cardiac myofibers are held together by connective tissue. Individual myofibers are surrounded by a delicate CT endomysium, with reticular and fine collagenous fibers (Fig. C14). The amount of CT between cells is significantly less than for skeletal muscle. A very rich capillary network is present. Myofibers are bundled into groups by a perimysium with collagenous fibers coarser than those of endomysium. The entire mass of cardiac muscle is surrounded by a covering of connective tissue.

  • C. Other Noteworthy Features of Cardiac Muscle Cells

    In addition to electrotonic coupling at intercalated discs, the heart has a specialized conduction system. Modified cardiac myocytes conduct impulses from the atrioventricular node through the ventricular septum into the ventricles. These cells, Purkinje fibers, exhibit cytoplasmic modifications consistent with their function; myofilaments form poorly organized myofibrils and transverse tubules are absent (Fig. C15-19).

    Atrial and ventricular cardiac muscle differs somewhat. In the atrium, muscle cells are a little smaller, and have fewer T-tubules. Atrial myocytes, particularly in the right atrium, produce atrial natriuretic factor (ANF), and have been shown to produce brain natriuretic factor (BNF) as well. These hormones act on the kidneys to stimulate sodium and water loss and thereby coordinate the regulation of blood pressure and body fluids. When the blood volume is expanded, ANF is secreted as a prohormone that is cleaved to form the active hormone (the carboxy terminal fragment). As expected, ANF is synthesized and transported through the ER-Golgi membranes, and the prohormone is stored in membrane bound granules, atrial granules, mostly located near the Golgi complex in the perinuclear cytoplasm (Fig. C20). Upon stimulation, the prohormone is secreted and processed to the active form.

 

IV. Smooth Muscle

 

Smooth muscle cells are non-striated and thus are very different in appearance from both skeletal and cardiac myofibers (Fig. C24-26). Smooth muscle is an involuntary muscle. The tapered cells have a central bulging nucleus and relatively homogenous cytoplasm. Smooth muscle is found in the walls of many hollow organs, e.g., viscera and blood vessels. The cells are small, with a diameter of 3-8 µm and a length of 15-200 µm.

  • A. Major Features of Smooth Muscle Cells (Figs. C24-27)
    • 1. Myofilaments, predominantly actin-containing thin filaments, are present in the cytoplasm, but are not as abundant as in striated muscle. The myofilaments are not arranged into sarcomeres and myofibrils, and cannot be seen in the light microscope. However, they are observed readily in the electron microscope (Figs. C27, 28).
    • 2. A single, central nucleus causes the cell to bulge in the middle and take on a fusiform appearance. In longitudinal section, the cells are usually staggered such that the nuclear portion of one fiber lies next to the tapered end of an adjacent fiber. Because of this staggered arrangement, in a cross section, the nuclei of only a portion of the cells can be seen (Fig. C24-25).
    • 3. Cytoplasmic organelles are largely confined to a conical region on each side of the nucleus (perinuclear cytoplasm). The organelles include mitochondria, Golgi apparatus, rough endoplasmic reticulum and free ribosomes. Glycogen and lipid droplets are observed (Fig. C27).
    • 4. A poorly elaborated sarcoplasmic reticulum, essentially equivalent to the smooth ER involved in Ca++ storage and regulation, is present in the cytoplasm of smooth muscle cells, and T-tubules are not found. There are abundant caveolae. Gap junctions between neighboring smooth muscle cells are common, particularly in visceral smooth muscle (Fig. C31).
    • 5. A prominent feature of smooth muscle cells observed at the EM level is the presence of dense bodies, fusiform densities in the sarcoplasm that contain -actinin and that are analogous to Z lines of striated myofibers (Figs. C29-31). These structures serve as anchorage sites for actin myofilaments, as do the attachment plaques, which are similar structures seen along the cytoplasmic surface of the sarcolemma. Desmin intermediate filaments are associated with these structures in all smooth muscle, and vimentin is an additional component in vascular smooth muscle.
  • B. Types of Smooth Muscles

    Smooth muscle cells are commonly in prominent sheets and bundles, and are also present as individual scattered cells or small bundles in connective tissue. Two main types of smooth muscles are recognized, visceral and multi-unit (C33).

    • 1. Visceral (unitary) smooth muscles are found in the walls of many hollow organs (e.g., blood vessels and parts of the digestive tract, uterus and urinary bladder). They characteristically exhibit sustained contractions or waves of contraction. Only a few of the smooth muscle cells are innervated. Cells are functionally connected by gap junctions, so that excitation of contraction can spread from cell to cell (Figs. C31-33). Depolarization (and thus contraction) occurs spontaneously or in response to hormones or physical stimuli (e.g., stretch). Nervous stimulation regulates contraction.
    • 2. Multi-unit smooth muscles rely primarily upon neural stimulation of contraction. Cells receive individual innervation. Smooth muscles of this type undergo relatively rapid, precisely graded contraction. Examples of multi-unit smooth muscles are the sphincter pupillae of eye and arrector pili muscles of skin.
  • C. Associated Connective Tissue

    Just as with skeletal and cardiac muscle, smooth muscle cells are held together by connective tissue (C34).

    • 1. Each smooth muscle cell is surrounded by a basal lamina that blends into a delicate network of reticular, elastic and fine collagenous fibers. In many cases, the cells are separated by only 50-80 nm, the intercellular space filled with fine connective tissue fibers. These fibers (where smooth muscle cells are very closely apposed) are produced by the smooth muscle cells themselves, rather than by fibroblasts.
    • 2. Smooth muscle cells are bundled into groups by coarser collagenous and elastic connective tissue fibers (produced by fibroblasts in that connective tissue). Capillaries and nerves are also present in these regions.

 

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