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Skeletal, or voluntary, muscle constitutes the principal organ of locomotion, as well as a vast metabolic reservoir. Disposed in more than 600 separate muscles, this tissue makes up as much as 40 percent of the weight of adult human beings. An intricacy of structure and function undoubtedly accounts for its diverse susceptibility to disease, for which reason the main anatomic and clinical facts are provided as an introduction to the following several chapters on muscle disease. The essential physiologic facts concerning the function of muscle are in Chap. 45 and those of the neuromuscular junction, in Chap. 53.

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A single muscle is composed of thousands of muscle fibers that extend for variable distances along its longitudinal axis. Each fiber is a relatively large and complex multinucleated cell varying in length from a few millimeters to several centimeters (34 cm in the human sartorius muscle) and in diameter from 10 to 100 μm. Some fibers span the entire length of the muscle; others are joined end to end by connective tissue. Each muscle fiber is enveloped by an inner plasma membrane (the sarcolemma) and an outer basement membrane. The multiple nuclei of each fiber, which are oriented parallel to its longitudinal axis and may number in the thousands, lie beneath the plasma membrane (sarcolemma); hence they are termed subsarcolemmal, or sarcolemmal nuclei.

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The cytoplasm (sarcoplasm) of the cell is abundant and contains myofibrils and various organelles such as mitochondria and ribosomes. Each myofibril is enveloped in a membranous net, the sarcoplasmic reticulum (SR; see Fig. 45-2). Extensions of the plasma membrane into the fiber form the transverse tubular system (T tubules), which are extracellular channels of communication with the intracellular sarcoplasmic reticulum. The SR and T tubules are anatomically independent but functionally related membrane systems. The junctional gap between the T tubules and SR is occupied by protein formations that are attached to the SR and are referred to as junctional feet; the latter have been identified as ryanodine receptors and are responsible for the release of calcium from the SR, which is a critical step in exciting the muscle (see Franzini-Armstrong).

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The myofibrils themselves are composed of longitudinally oriented interdigitating filaments (myofilaments) of contractile proteins (actin and myosin), additional structural proteins (titin and nebulin), and regulatory proteins (tropomyosin and troponin). The series of biochemical events by which these proteins, under the influence of calcium ions, accomplish the contraction and relaxation of muscle is described in Chap. 45. Droplets of stored fat, glycogen, various proteins, many enzymes, and myoglobin, the latter imparting the red color to muscle, are contained within the sarcoplasm or its organelles.

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Although the muscle fiber represents an indivisible anatomic and physiologic unit, disease may affect only one part of it, leaving only that part, or sometimes the remainder, to become dysfunctional or to atrophy, degenerate, or regenerate, depending on the nature and severity of the disease ...

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