Skeletal Muscle PDF

_____________ LESSON 10 _____________ SKELETAL MUSCLE I. GENERAL Muscle tissue is a highly specialized tissue, made up of muscle cells with large amounts of contractile proteins (actin and myosin) and, therefore, can contract in a coordinated way in a certain direction to produce movement. Due to...

_____________ LESSON 10 _____________ SKELETAL MUSCLE I. GENERAL Muscle tissue is a highly specialized tissue, made up of muscle cells with large amounts of contractile proteins (actin and myosin) and, therefore, can contract in a coordinated way in a certain direction to produce movement. Due to the elongated morphology of muscle cells, they are called muscle fibers or myofibers. These are arranged parallel to each other to form bundles of fibers oriented in the direction of contraction. According to the morphological and functional characteristics, both muscle fibers and their arrangement to form a tissue, three varieties are differentiated: • Skeletal muscle: it is part of the musculoskeletal system and certain organs, such as the tongue and the eyeball. The muscle fibers present transverse striations in the cytoplasm. Contraction is voluntary. • Cardiac muscle: form the heart muscle, the myocardium. Its muscle fibers have transverse striations in the cytoplasm, and although the term "striated muscle" includes both skeletal muscle and cardiac muscle, it is often used to designate skeletal muscle. Contraction is involuntary and rhythmic. • Smooth muscle: it is part of the viscera and blood vessel wall, among other locations. The smooth muscle fibers do not exhibit crossstriations in the cytoplasm. Contraction is involuntary. The cells of the different muscle varieties are externally enveloped by a thick outer sheath, a external lamina, very similar to a basement membrane, to which the contraction movement of the contractile proteins is transmitted, through binding proteins arranged in the cell membrane. In a general way, the name of the different organoids and muscular structures is preceded by the prefix “sarco”, which has the Greek meaning of muscular. Thus, the cytoplasmic membrane of muscle cells is called sarcolemma; the cytoplasm sarcoplasm, the endoplasmic reticulum sarcoplasmic reticulum, or the mitochondrion sarcosome. 1 II. SKELETAL MUSCLE Skeletal muscle is made up of muscle fibers of cylindrical morphology, whose size is highly variable, between 10-120 m in diameter, and with great length, some are as long as the muscles of which they are part. The size of muscle fibers varies with age, exercise, nutritional status, gender and the position of the fiber within the muscle. Each muscle fiber is surrounded by a thin layer of reticular connective tissue called endomysium, which contains numerous capillaries and nerve fibers. Muscle fibers are grouped in parallel in fascicles whose thickness varies according to muscle activity and every bundle is surrounded by connective tissue septa with abundant collagen fibers, capillaries and nerve fibers and is called perimysium. The fascicles are grouped forming muscles and are surrounded by a band of dense irregular connective tissue with abundant collagen fibers type I and II and elastic fibers called epimysium, which is continuous with the tendons and muscle attachments. Through the epimysium, the arteries and nerves penetrate the muscles, branching out through the perimysium and endomysium to carry irrigation and innervation to the muscle fibers. Figure 1. Structure of skeletal muscle (adapted from Gartner and Hiat, 2013, Color Atlas and Text of Histology, 6th Ed.). The origin of skeletal striated muscle fibers is the fusion of numerous myoblasts, which are immature cells originating from the mesoderm and have fusiform morphology. The morphology of skeletal striated muscle fibers in fresh in a cross-section is rounded, but when fixed they appear with polygonal morphology. These muscle fibers have numerous nuclei, oval and located on the periphery of each muscle fiber, aligned under the sarcolemma. Near the tendon junctions, it is normal to find some nuclei inside the sarcoplasm. 2 Figure 2. Structure of skeletal muscle (adapted from Gartner and Hiat, 2013, Color Atlas and Text of Histology, 6th Ed.). The plasma membrane of muscle fibers is called sarcolemma, as mentioned above, and in skeletal muscle presents invaginations called T tubules. Each T tubule is associated with two terminal cisternae of the highly developed smooth sarcoplasmic reticulum and forms the structure called the triad. The triads are of great importance for the regulation of muscle contraction and embrace the bundles of myofibrils at regular intervals. In mammals they coincide with the transitions between A and I bands. The T tubules allow the depolarization of the sarcolemma to reach deep regions of the cytoplasm, inducing the exit of Ca ++ from the terminal cisterns of the sarcoplasmic reticulum, which initiates the mechanism of muscle contraction. The sarcolemma has caveolae that correspond to pinocytosis vesicles. It also has depressions where the terminal button of the neuron makes the nerve synapse with the muscle fibers, constituting the motor units, and other depressions where the satellite cells are located. The satellite cells exhibit an oval nucleus and scant cytoplasm where a few mitochondria and little tubular system appear and are characterized as having the ability to divide and fuse to the muscle fibers to increase their thickness and are capable of regenerating damaged muscles fibers if they do not have the external lamina damaged. Regenerated fibers differ from normal fibers because they have nuclei in the center rather than on the periphery. The satellite cell population is high in young animals and decreases with age. 3 The sarcoplasm is intensely eosinophilic and as organelles has sarcoplasmic reticulum, numerous mitochondria or sarcosomes, which are arranged along the bundles of myofibrils, as well as glycogen  granules, which constitute the main source of energy for the muscle contraction. Often, small lipid vacuoles which store triglycerides as an energy source are also observed. At the poles of each nucleus small Golgi complexes can be found. Within the sarcoplasm we can also find non-contractile proteins such as albumin and myoglobin molecules, which give the muscle its characteristic red color. The function of these myoglobin molecules is to store oxygen that will be used in anaerobic glycolysis to obtain energy during muscle contraction. Mineral salts can also be found. Most of the sarcoplasm (60-70% of the volume) is occupied by myofibrils, which measure is 1-2 µm in diameter. In longitudinal sections, the myofibrils show highly refractive transverse striations that stain strongly with iron hematoxylin. The myofibrils are composed, mainly, by contractile proteins: actin, the thin myofilaments (7 nm in thickness approximately) and myosin, the thick myofilaments (about 15 nm of thickness approximately). In skeletal and cardiac muscles myofilaments have a characteristic arrangement which results in the transverse striations observed by light microscopy. 1. Structure and ultrastructure of myofibrils With the polarized light microscopy, the muscle fibers show a striation with anisotropic bands, highly refractive, (A band) alternating with isotropic bands, without refringence, (I band). With the electron microscopy, A band is electrondense and is composed of thick and thin myofilaments, while I band shows low electron-density and is formed only by thin myofilaments. In the center of the I band there is an electron-dense line (Z line), where the thin myofilaments are fixed by a protein called -actinin. The structure between two Z lines is called sarcomere, and it is the unit of muscle contraction. In the center of the A band there is another smaller band with a lower electron-density, composed exclusively of thick myofilaments and called H band. In the center of the H band there is another electron-dense line (although less than the Z line) called M line, to which the thick myofilaments are anchored by various proteins. In the cross sections, at the level of A band, it is observed that each thick myofilament is surrounded by 6 thin myofilaments (Fig. 2). This arrangement of thick and thin myofilaments is maintained by intermediate filaments of vimentin and desmin, which bind to the Z lines and the sarcolemma, while dystrophin binds actin to the sarcolemma, which in turn is bound to glycoproteins of the external lamina to which they transmit movement during muscle contraction. Thin myofilaments are composed of molecules of fibrous or F actin consisting of molecules of globular or G actin which polymerize to form a double helix. Each G-actin molecule has an active myosin-binding site. Along the actin double helix, a fibrillar protein called tropomyosin appears, which in the resting situation covers the active binding sites with myosin. A globular protein called troponin also appears at regular intervals, is made up of three globular polypeptides, TnT, which binds tropomyosin, TnC, which has a high affinity for 4 calcium, and TnI, which inhibits actin-myosin binding. Another protein called nebulin helps maintain the actin arrangement in the sarcomere. Thick myofilaments consists of 200 to 300 myosin II molecules, and each molecule is composed of two identical heavy chains (resemble two golf clubs) and two pairs of light chains. B A C Figure 3. Striated muscle fiber under the light microscope (A) and (B) and under the electron microscope (C). 2. Mechanism of skeletal muscle contraction Muscle contraction begins when Ca++ is released from the sarcoplasmic reticulum. As its concentration increases in the cytoplasm, it binds to the TnC unit of actin, causing a change in conformation and dragging TnI and tropomyosin, leaving the active actin-myosin binding site free. This binding occurs immediately, which activates the ATPase at the myosin head. The consumption of one molecule of ATP results in a conformational change of myosin, which acts as a hinge dragging actin. The actin-myosin union is then broken, and the myosin head is ready to bind to actin again. This cycle is repeated hundreds of times per second, so that the thin myofilaments are pulled along by the myosin heads and entering the thick myofilaments. The result is that the sarcomere is shortened and the sum of the shortening of all the sarcomeres of all the myofibrils of a muscle produces a shortening of it, and when a group of muscle cells is shortened, they cause the shortening of the muscle as a whole, which it will transmit movement to the bones or structures into which it is attached. Skeletal muscle contracts according to the "all or none law": each cell may or may not contract, and it is the number of muscle cells that contract at the same time in a muscle that will determine the intensity of the muscle's contraction. When Ca++ returns to the sarcoplasmic reticulum, by means of a dependent Ca - Mg + + pump, with energy consumption, troponin returns to its initial place, preventing actin-myosin binding, so the filaments return to their position of origin. The contraction of the muscles that occurs several hours after death (rigor mortis) is due to the depletion of ATP, so the Ca ++ - Mg + + pump stops working and the Ca ++ ions cannot enter the sarcoplasmic reticulum and thus the myosin filaments cannot be separated from actin and muscles remain contracted permanently. ++ Muscle contraction is regulated by the innervation of motor neurons. Skeletal muscle fibers are innervated by motor neurons through endings called neuromuscular plates. These motor neurons are located in the ventral horns of 5 the spinal cord. Each motor neuron innervates a group, between 10 and 1000, of muscle fibers, which contract at the same time. The motor neuron and the group of muscle fibers innervated by it is called the motor unit. According to the structure and morphological and functional characteristics, several types of motor units can be differentiated: • S or slow motor unit: it is made up of type I or slow muscle fibers, which are muscle fibers that have a high myoglobin content, are slow and sustained contraction for long periods of time and are nonfatigable fibers. These types of fibers are rich in mitochondria, have a thick Z line and a low smooth sarcoplasmic reticulum. • FR motor unit: is made up of type IIA or intermediate fibers, since they have an intermediate myoglobin content, are fastcontracting and fatigue-resistant. These fibers are rich in mitochondria, their Z line is thick, and the smooth sarcoplasmic reticulum is scarce. • FF motor unit: it is made up of type IIB or white fibers, as they have a low myoglobin content, are fast-contracting, intervene in rapid force movements and fast fatigable. These fibers have few mitochondria, their Z line is thin, and they have a highly developed sarcoplasmic reticulum. When the motor neuron sends a nerve impulse to the neuromuscular plate, acetylcholine is released, which binds to receptors in the sarcolemma producing a depolarization of this membrane, which is transmitted through the T tubules, causing a massive outflow of Ca ++ from the sarcoplasmic reticulum, which triggers muscle contraction. If more nerve impulses are not produced, a acetylcholinesterase present in the basal lamina surrounding the sarcolemma degrades acetylcholine, ceasing the sarcolemma depolarization, which pump Ca ++ -Mg++ introduces Ca ++ within the sarcoplasmic reticulum where it is retained by a protein, calsequestrin, ceasing muscle contraction. Skeletal muscles are subject to a reflex contraction to maintain muscle tone, which is determined by the muscle spindles. These spindles are encapsulated sensory receptors compounds by 8-10 modified muscle fibers surrounded by connective capsules. 6