Overview – Muscle
Plate 7-1. The Skeletal Muscle Fiber
Plate 7-2. Skeletal Muscle: The Sarcomere
Plate 7-3. The Heart: Cardiac Muscle
Plate 7-4. Smooth Muscle
The microanatomy of muscle is particularly fascinating in that the function of a muscle cell is clearly manifest in its ultrastructure. The most significant feature of a muscle cell, usually called a muscle Fiber, is that it can change its shape rapidly, repeatedly, and predictably unlike most other cells in the body.
Cellular motility is one of the most extensively investigated phenomena in modern cell biology, and for good reason. Virtually all cells that have been studied display some capacity for movement, whether they move themselves in space, change their shape, or shuttle submicroscopic components about in their Cytoplasm. What places muscle in a class by itself is that muscle cells have developed a tremendous Hypertrophy of a macromolecular motile mechanism that is present, albeit on a smaller scale, in the majority of other somatic cells.
The three major histologic categories of muscle in the human body are Skeletal Muscle, cardiac muscle, and Smooth Muscle. Skeletal Muscle, also called striated muscle, is innervated by motor nerves and is responsible for voluntary bodily movements. Cardiac muscle constitutes the bulk of the tissue of the heart and provides the contractile force that permits that organ to pump great volumes of blood with high speed and efficiency. Smooth Muscle, innervated by the autonomic nervous system, provides the motive force for involuntary movements of organs such as the stomach, intestines, and blood vessels. Whereas skeletal and cardiac muscle are somewhat similar in ultrastructure, Smooth Muscle is in a class by itself.
Perhaps the most difficult concept in the microanatomic organization of Skeletal Muscle is the structural hierarchy of its components. Figure 7-1 demonstrates the architecture of Skeletal Muscle. Here, it is apparent that a whole muscle – a bicep, in this case – contains bundles of individual muscle fibers. Each muscle Fiber is a discrete unit surrounded by its own Plasma membrane. In muscle, the Plasmamembrane is often called the Sarcolemma. By cellular standards, the Skeletal Muscle Fiber is huge; it measures up to 0.1 mm (100 Â µm) in diameter and can reach many centimeters in length (Table 7-1). Each muscle Fiber is a Syncytium – one cell derived from many cells that came to be enveloped by a common Plasmamembrane.
TABLE 7-1. Typical Dimensions of Skeletal Muscle Fibers
Each individual muscle Fiber is subdivided into many longitudinally oriented units called myofibrils. Each Myofibril, in turn, is surrounded by a network of the smooth Endoplasmic Reticulum called the Sarcoplasmic Reticulum. Each Myofibril runs from one end of the muscle Fiber to the other and is periodically subdivided along its length into contractile units called sarcomeres. Each Sarcomere measures about 2.5 Â µm in length and consists of an orderly array of Actin and Myosin filaments. The Actin and Myosin filaments, called myofilaments, are carefully arranged so they can slide over one another during the process of muscle contraction. The ends of each Sarcomere are capped by Z-bands (also called Z-lines or Z-disks). Actin filaments insert into the material of the Z-bands. Myosin filaments lie between the Actin filaments and physically interact with them via tiny Myosin cross-bridges – the ATPase-containing heads of the heavy Meromyosin portion of the Myosin molecule. Under appropriate conditions of neuronal stimulation, portions of the sarcoplasmic reticulurn release calcium ions, which promote local hydrolysis of ATP, causing the Myosin crossbridges to move and thus forcing the Actin filaments to slide over the Myosin filaments. The Actin filaments attached to the Z-bands at the opposite ends of the Sarcomere draw the Z-bands close to one another, thus shortening the length of the Sarcomere and of the muscle Fiber itself.
Like Skeletal Muscle, cardiac muscle is made up of fibers composed of many parallel myofibrils. Each Myofibril is constructed of a series of sacromeres aligned end to end along its length. Cardiac muscle fibers, however, are significantly different from Skeletal Muscle fibers in several important ways. First, cardiac muscle fibers are much smaller than Skeletal Muscle fibers and contain only 1 or 2 nuclei (as opposed to 100 to 1000 nuclei in a Skeletal Muscle Fiber). Second, cardiac muscle fibers are branched. The branches of one cardiac muscle Fiberattach to the branches of neighboring cardiac muscle fibers by highly specialized intercellular junctions called intercalated disks.
Smooth muscle, as its name suggests, is devoid of the obvious striations observed in skeletal and cardiac muscle. Smooth Muscle cells, or fibers, are small and mononucleate. Their contractile apparatus consists of Actin and Myosin filaments, but the myofilaments are not organized into sarcomeres; neither is the Cytoplasmof Smooth Muscle fibers subdivided into myofibrils. Although the precise organization of the myofilaments (and hence the mechanism of contraction) is not yet fully understood in Smooth Muscle, it is certain that Actin and Myosin are present and do interact to effect significant changes in length of the Smooth Muscle Fiber.
The Skeletal Muscle Fiber
Human beings are capable of a wide range of movements, from the powerful movements of a weightlifter hoisting a barbell to the delicate finger movements of an eye surgeon performing a corneal transplant. Skeletal muscles power these voluntary movements. Whether the voluntary movements involve large muscles, like the thigh muscles of the weightlifter, or tiny muscles, like the finger muscles of the eye surgeon, the same unit of function, the Skeletal Muscle Fiber, is responsible for voluntary movements. Taken together, all of the Skeletal Musclefibers constitute approximately one half of a person’s total body mass.
Each Skeletal Muscle Fiber is actually a single cell – a huge, cylindric, Multinucleate cell, quite different from any reviewed so far. Whereas most cells measure some 20 Â µm in diameter and have but a single Nucleus, a typical Skeletal Muscle Fiber may measure 100 Â µm in diameter and up to 30 cm in length and may contain several thousand nuclei. A single cell can be that large because of its genesis in the early embryo, in which each Skeletal Muscle Fiberforms as a Syncytium, a cell with many nuclei that is surrounded by a single Plasma membrane.
The Multinucleate nature of the muscle Fiber takes its origin in early development, in which many embryonic muscle cells, called myoblasts, line up end to end to form long, thin myotubes. At a given time, the Plasma membranes that separate adjacent myoblasts along the length of the tube fuse, and the cells become surrounded by a single membrane and thus take the form of a true Syncytium.
Portions of several mature human Skeletal Muscle fibers, labeled F1 and F2, are illustrated in the matched pair of light and electron micrographs at right. Here, the perimeter of one muscle Fiber (F2) is indicated by dotted lines. (Their ends, however, cannot be shown; skeletal muscle fibers, measuring several centimeters in length, are far too long to fit into one field of view.) The space between adjacent muscle fibers (arrow) is filled with a thin layer of connective tissue that envelops each muscle Fiber. This connective tissue envelope, called the Endomysium, surrounds the Plasma membrane of the muscle cell, the Sarcolemma. The Sarcolemma is an Excitable Membrane; it can conduct electrical excitation, brought in by a nerve Fiber, all over the surface of the muscle Fiber. This conduction, as we shall see, is central to the control of the process of muscle contraction.
When viewed with the light microscope, as in Figure A, one of the most prominent features of Skeletal Muscle is manifest in the periodic striations along its length. The nature of these striations is clarified by electron microscopy in Figure B. The striations reflect the orderly arrangement of protein filaments called myofilaments that fill the Cytoplasm of the muscle Fiber. These myofilaments are composed largely of two proteins: Actin and Myosin. Traditionally-and erroneously-referred to as contractile proteins, Actin and Myosin are organized in a highly specific manner into contractile units, myofibrils. Myofibrils, in turn, are composed of units of function, sarcomeres. The structure and function of the Sarcomere, described in the overview, is illustrated in Plate 7-2.
Most cells are capable of cytoplasmic movements of one sort or another. Many of these movements involve interactions between Actin and Myosin. In most cells, however, the actomyosin complexes are diffuse and do not form the most conspicuous part of the cell. In Skeletal Muscle, the reverse is true. A tremendous Hypertrophy of the actomyosin system has taken place, and virtually all of the cytoplasmic volume is occupied by these contractile proteins. Even the nuclei (N), central and prominent in most cells, are pushed off to the side in Skeletal Musclefibers. Mitochondria, however, are plentiful, and modifications of the endoplasmic reticulum are abundant. These will be shown at higher magnification later in this chapter.
Plate 7-1, Figures A and B. Matched pair of light and electron micrographs of serial longitudinal sections taken through the sternocleidomastoid muscles of the neck of an adult man. F1, F2, individual Skeletal Muscle fibers; N, peripherally located Nucleus; dotted lines, perimeter of muscle Fiber, F2; arrows, Endomysium. Figure A, 2,350 X; Figure B, 2,800 X
Skeletal Muscle: The Sarcomere
The Sarcomere is the fundamental unit of contraction of the Skeletal Muscle Fiber. In order to clearly understand the nature of the Sarcomere, it is important first to understand the nature of the Myofibril, in which the sarcomeres are aligned. A single Skeletal Muscle Fiber consists of many myofibrils packed together in parallel, much like a jar filled with straws (Figure 7-1). Each long, thin, cylindric Myofibril runs the entire length of the muscle Fiber, separated from adjacent myofibrils by a system of membranes called the Sarcoplasmic Reticulum. A Myofibril consists of a series of sarcomeres lined up end to end along the length of the Myofibril. Figure A, a longitudinal section through a human Skeletal MuscleFiber, contains many myofibrils side by side; one Myofibril is outlined by a dotted line. Many dark transverse Z-bands, which mark the ends of the sarcomeres, are arranged periodically along its length. Several sarcomeres are shown at high magnification in Figure B. Here, the Z-band (Z) appears as a somewhat amorphous, electron-dense structure. Next to the Z-band is the I-band (I), which contains Actin filaments. Between the I-bands is the A-band (A), a dense region of the Sarcomere that contains both Actin and Myosin filaments. (To get a better impression of the arrangement of Actin and Myosin filaments, see Figure C, a cross section through the A-band). In the center of the A-band is a somewhat less dense region called the H-zone. As shown in Figure 7-1, each Sarcomere shortens during muscle contraction. This shortening is accomplished by the relative sliding of Actin and Myosin filaments over one another. When the Actin filaments (in the I-band) and the Myosin filaments (in the A-band) slide over one another, the Z-bands are drawn closer together, the Sarcomere actively decreases in length, and, as a result of collective Sarcomere action, the whole muscle Fiber shortens.
A Sarcomere in a partially contracted state is shown in Figure D; note that the I-bands (I) have all but disappeared. A corduroy-like pattern is evident in the A-band (A). This pattern reflects the presence of cross-bridges between the thin Actinfilaments and the thick Myosin filaments as they lie side by side in the A-band. These cross-bridges represent the movable part of the Myosin molecules, which, in response to ATP, move back and forth in a ratchetlike fashion, producing the motive force for muscle contraction.
Two separate membrane systems are important in the control of muscle contraction: the sarcoplasmic reticulum and the T-System. As shown in Figure D, the terminal Cisternae of the Sarcoplasmic Reticulum (SR) and a tubule of the T-System (T) are grouped together in a structure called the triad (dotted circle). Their structural grouping is functionally significant for several reasons. The terminal Cisternae of the sarcoplasmic reticulum, which represent modifications of the smooth Endoplasmic Reticulum, can selectively take up and release calcium ion. Tubules of the T-System, which are invaginations of the Sarcolemma (Plasmamembrane), can carry electrical excitation from the cell surface into the inner reaches of the muscle Fiber. When a nerve stimulates a muscle, the electrical excitation travels inward along the T-System. The electron excitation causes the adjacent Sarcoplasmic Reticulum to release calcium, which triggers the process of muscle contraction by activating the ATPase on the Myosin cross-bridges. ATPhydrolysis is followed by crossbridge movement which, in turn, generates the force for muscle contraction.
Plate 7-2, Figure A. Longitudinal section through human Skeletal Muscle. N, Nucleus of muscle Fiber; Z, Z-band; dotted line, outline of single Myofibril; brackets, limits of one Sarcomere. 11,000 X
Figure B. Electron micrograph of sarcomeres within longitudinal section of relaxed human Skeletal Muscle. A, A-band; H, H-zone; I, I-band; M, mitochondrion; SR, Sarcoplasmic Reticulum; Z, Z-band. 35,500 X
Figure C. Cross section of Myofibril of human Skeletal Muscle through A-band of Sarcomere. A, A-band; SR, sarcoplasruic reticulum; dotted line, outline of single Myofibril; arrow, “thick” (Myosin) filament; arrowhead, “thin” (actifl) filament. 84,000 X
Figure D. Longitudinal section through partially contracted Sarcomere. A, A-band; 1, shortened I-band; M, mitochondrion; SR, terminal cisterna of Sarcoplasmic Reticulum; T, tubule of T-System; Z, Z-band; dotted line encircles triad. 52,000 X 78
The Heart: Cardiac Muscle
The human heart is a powerful pump that propels blood to all parts of the body rapidly. During strenuous exercise, for example, the left ventricle of the heart is capable of pumping 12 gal/min into the aorta. This flow rate is greater than that of a garden hose turned on full. The tremendous pumping force of the heart is generated by a special kind of muscle called cardiac muscle. Cardiac muscle is similar to Skeletal Muscle in that it is striated, its fibers are organized into myofibrils, and the fundamental unit of contraction is the Sarcomere. There are, however, many significant differences between cardiac and Skeletal Muscle, as seen in Figures A and B.
Figure A is a low-magnification electron micrograph of a cross section through the Atrium of the heart of the squirrel monkey. The wall of the heart, like that of large blood vessels, consists of three distinct regions. The innermost region that lines the lumen (L) of the heart, the Endocardium (EN), consists of a thin layer of endothelial cells and some loose connective tissue. Most of the mass of the heart is contained within the muscular Myocardium (MYO). The outermost region of the wall of the heart is the Epicardium (EPI), an envelope of dense connective tissue containing both collagenous and elastic fibers.
The contractile force of the Myocardium is supplied by cardiac muscle fibers. Unlike the Skeletal Muscle Fiber, which is a Syncytium, each Cardiac Muscle Fiber consists of a number of branched cardiac muscle cells aligned end to end. Consequently, each Cardiac Muscle Cell – which measures around 100 Â µm in length and 15 Â µm in width – is much smaller than a typical Skeletal MuscleFiber. The size of a Cardiac Muscle Cell is evident in Figure A, in which the lateral boundaries of a single cell are marked with a dotted line.
The details of cardiac muscle microanatomy are illustrated in Figure B, a higher magnification electron micrograph of the Myocardium of the monkey heart. Here, as in Figure A, the lateral boundaries of a single Cardiac Muscle Cell are indicated by a dotted line. Within this cell, several longitudinally oriented myofibrils (MF) are marked by brackets. As in Skeletal Muscle, each Myofibril consists of a series of contractile units, or sarcomeres, aligned end to end. Numerous Mitochondria(M) are present between adjacent myofibrils. These large, abundant Mitochondriasupply the ATP essential for muscle contraction, which, in cardiac muscle, must occur many times per minute for life to go on.
One of the most interesting features of cardiac muscle is the specialized junctions-the intercalated disks-by which cardiac muscle cells contact and adhere to one another. As mentioned previously cardiac muscle cells are branched. The branches of one Cardiac Muscle Cell join the branches of another muscle cell in such a way that the cells are linked end to end. The Intercalated Disk (ID), a dense line, is evident where the branches meet, as illustrated in Figure B. It performs several important functions. First, it acts as an adhesive structure that holds together the tips of abutting branches of adjacent cardiac muscle cells, thus preventing them from being pulled apart when the muscle Fiber contracts. Second, it provides for electrical continuity between adjacent cardiac muscle cells; that is, ionic currents may pass freely from one cell to another through specialized regions within the Intercalated Disk.
The Intercalated Disk is capable of performing several functions because it contains several different kinds of intercellular junctions. Intermediate junctions perform an adhesive function. Gap junctions allow certain ions to pass, providing electrical continuity between adjacent cells. Desmosomes act as “spot welds,” also serving to hold the adjacent cells together. Taken together, the intercalated disks allow the individual cells within a Cardiac Muscle Fiber to act together as if they were a Syncytium.
Plate 7-3, Figure A. Electron micrograph of cross section through the Atrium of the squirrel monkey heart. CT, connective tissue; EN, Endocardium; EPI, Epicardium; L, lumen of Atrium; MYO, Myocardium; dotted line, outline of individual Cardiac Muscle Cell. 2,800 X
Figure B. Longitudinal section through portions of several cardiac muscle fibers. A, A-band; Co, Collagen fibrils; 1, I-band; ID, Intercalated Disk; M, Mitochondria; MF, Myofibril; Z, Z-line; dotted line, outline of individual Cardiac Muscle Cell. 16,000 X 80
Smooth muscle is quite different in structure and function from skeletal and cardiac muscle in several important respects. When viewed with the light or electron microscope, Smooth Muscle displays no striations. A given Smooth Muscle Fiber is quite small (averaging some 5 to 10 Am in width and 20 to 200 um in length), tends to contract rather slowly, and has only one centrally located Nucleus. Instead of being associated with the voluntary movements of the outer body, as is Skeletal Muscle, or with the rhythmic contractions of the heart, as is cardiac muscle, smooth muscle tends to be associated with the involuntary movements of the viscera, respiratory system, and circulatory system.
In the alimentary canal, for example, Smooth Muscle is responsible for the peristaltic movements that propel food on its course as it undergoes the process of digestion. The position of Smooth Muscle within the wall of the intestine is illustrated by light microscopy in Figure A. Here, the Smooth Muscle fibers are organized into two distinct sheets running at right angles. The inner circular layer of Smooth Muscle is shown in cross section (XS); the outer longitudinal layer is shown in long section (LS). Since each Smooth Muscle Fiber is fusiform, or spindle-shaped, it will look more or less circular when cut in cross section and long and thin when cut lengthwise. This difference is more clearly shown in Figure B, an electron micrograph of a serial section cut from the same specimen depicted in Figure A. Here, each Smooth Muscle Fiber is surrounded by connective tissue (CT) that serves to bind the individual fibers into a functional sheet of Smooth Muscle tissue. In this field of view, small autonomic nerves (N) that innervate the Smooth Muscle are evident, as are blood capillaries (C) and lymph capillaries (LC).
Portions of several Smooth Muscle fibers are shown at higher magnification by electron microscopy in Figures C and D. Figure C, a longitudinal section, shows the centrally located Nucleus (N) surrounded by Cytoplasm that contains many fine filaments. These filaments, called myofilaments, resemble the thin Actinfilaments observed in skeletal and cardiac muscle. A glance at Figure C shows at once that Smooth Muscle is not organized neatly into sarcomeres. Although many studies have revealed the presence of both Actin and Myosin within Smooth Muscle, the precise relative arrangement of Actin and Myosin within the smooth muscle Fiber awaits discovery.
Figure D is a cross section of a single Smooth Muscle Fiber taken through the center of the cell at the level of the Nucleus (N). The Nucleus is folded upon itself, suggesting that the cell was fixed in the contracted state. The thin filaments, presumably made of Actin, are evident everywhere. A few thick filaments, which may represent Myosin, are detectable. At the periphery of the cell, a number of dense bodies (D) are intimately associated with the Plasma membrane. Many workers in the field think that these dense bodies provide attachment sites for the myofilaments. During the process of Smooth Muscle contraction, the myofilaments pull against these dense bodies. Because the dense bodies are attached to the Plasma membrane, the cell shortens. When the cell contracts, a number of pits, called Caveolae (arrows), become evident at the cell surface. Outside of the Plasma membrane, the smooth muscle Fiber is covered by a Glycoprotein coat similar to the Basement Membrane (*) that is closely associated with fine Collagen fibrils (Co).
Plate 7-4, Figures A and B. Light and electron micrographs of Smooth Musclein the wall of the small intestine of the macaque. C, capillary; CT, connective tissue; LC, lymphatic capillary (Figure B only); LS, Smooth Muscle in longitudinal section; N, nerve; XS, Smooth Muscle in cross section; Figure A, 710 X;
Figure B, 1,300 X