CHAPTER Muscle Tissue usdle tissue, the fourth basic tissue type with epi- thelia, connective tissues, and nervous tissue, is composed of cells that optimize the universal cell property of contractility. Asin all cells, actin microfilaments and associated proteins generate the forces necessary for the ‘muscle contraction, which drives movement within organ s95- tems, of blood, and of the body as a whole. Essentially all ‘muscle cells are of mesodermal origin and differentiate by a gradual process of cell lengthening with abundant synthesis of the myofibrillar proteins actin and myosin. ‘Three types of muscle tissue can be distinguished fon the basis of morphologic and functional characteris- tics (Figure 10-1), with the structure of each adapted to its physiologic role # Skeletal muscle contains bundles of very long, multinucleated cells with cross-striations. Their contraction is quick, forceful, and usually under voluntary control * Cardiac muscle also has cross-striations and is com- posed of elongated, often branched cells bound to one another at structures called intercalated discs that are ‘unique to cardiac muscle. Contraction is involuntary, vigorous, and rhythmic. = Smooth muscle consists of collections of fusiform cells that lack striations and have slow, involuntary contractions. In all types of muscle, contraction is caused by the slid- ing interaction of thick myosin filaments along thin actin fla- ‘ments. "The forces necessary for sliding are generated by other ‘proteins affecting the weak interactions in the bridges between actin and myosin, As with neurons, muscle specialists refer to certain mus- cle cell organelles with special names, The cytoplasm of muscle cells is often called sarcoplasm (Gr. sarkos, flesh + plasma, thing formed), the smooth ER is the sarcoplasmic reticu- lum, and the muscle cell membrane and its external lamina are the sarcolemma (sarkos + Gr. emma, husk). fread ‘The variation n diameter of muscle flbers depends on fac- tors such as the specific muscle, age, gender, nutritional status, and physical training ofthe individual. Exercise ‘enlarges the skeletal musculature by stimulating formation fof new myotibrils and growth in the diameter of individual muscle fibers. This process, characterized by increased cell volume, is called hypertrophy (Gr. hyper, above + tropho, nourishment). Tissue growth by an increase in the hhumber of cells is termed hyperplasia (hyper + Gr. plasis, ‘molding, which takes place very readily in smooth muscle, ‘whose cells have not lost the capacity to divide by mitosis. > SKELETAL MUSCLE ‘Skeletal (or striated) muscle consists of muscle fibers, ‘which are long, cylindrical multinucleated cells with diameters of 10 to 100 um. During embryonic muscle development, mes- enchymal myoblasts (L. myo, muscle) fuse, forming myo- tubes with many nuclei, Myotubes then further differentiate to 191.192 CHAPTER I0 = Muscle Tasue 1 Skeletal muscle Light micrographs of each ype, acoompanied by ‘drawings. (a) Skeletal musele |s composed of | ‘gated, multinucleated fbers that show strong, quick, voluntary Contractions. (b) Cardlae musele Is composed of regular branched cells bound together longtucinally y intercalated form striated muscle fibers (Figure 10-2). Hlongated nuclei are found peripherally just under the sarcolemma, a characteristic ‘nuclear location unique to skeletal muscle fibers/cells, A small population of reserve progenitor cells called muscle satellite ‘cells remains adjacent to most fibers of differentiated skeletal smusde. Organization of a Skeletal Musc! ‘Thin layers of connective tissue surround and organize the contractile fibers in all three types of muscle, and these lay- ers are seen particularly well in skeletal muscle (Figures 10-3, and 10-4), The organization given by these supportive layers, resembles that in large peripheral nerves = The epimysium, an external sheath of dense connective tissue, surrounds the entire muscle. Septa of this tissue extend inward, carrying the larger nerves, blood vessels, and lymphatic of the muscle "= The perimysium is a thin connective tissue layer that immediately surrounds each bundle of muscle fibers Smoot muscle dlises and shows strong, Involuntary contractions. {e) Smeoth imusele is composed of grouped, fusiform cells with weak, involuntary contractions. The density of intercellular packing, seen reflects the small amount af extracellular connective tissue present. (a,b): X200. (c): X300. All HEE. termed a fascicle (Figure 10-3). Each fascicle of muscle fibers makes up a functional unit in which the fibers work together: Nerves, blood vessels, and lymphatics pen- cate the perimysium to supply each fscicle Within fascicles avery tin, delicate layer of reticu- Jar fibers and scattered fibroblasts, the endomysium, surrounds the external lamina of individual muscle fibers. In addition to nerve fibers, capillaries form a rich network inthe endomysium bringing O, to the muscle fibers (Figure 10-5). Collagen in these connective tissue layers of muscle serve to transmit the mechanical forces generated by the contract- ing muscle cells fibers; individual muscle fibers seldom extend from one end of a muscle to the other. Some skeletal muscles taper at their ends, where the epi- -mysium is continuous with the dense regular connective tis- sue of a tendon at myotendinous junctions (Figure 10-6) Ultrastructural studies show that in these transitional regions, collagen fibers from the tendon insert themselves among, ‘muscle fibers and associate directly with complex infoldings of sarcolemma,SPs Bee ene — mbes Satelite cell Diterentiaton Satelite cel Muscle fiver ‘Skeletal muscle begins to differentiate when mesenchymal els, called myoblasts, align and fuse together to make longer, multinucleated tubes called myotubes. Myotubes ‘synthesize the proteins to make up myoflaments and gradually bogin to show cross-stiations by light micros 093, Myotubes continue differentiating to form functional ‘nyotilaments, and the nuclei are displaced against the ‘sarcolemma, Part ofthe myoblast population does not fuse ane citfr: centiate but remains as a group of mesenchymal cells called ‘muscle satelite eells located on the external surface of ‘muscle floes inside the developing external lamina. Sate: Ite cells proliferate and produce new muscle fibers fellow. Jing muscle injury. Organization Within Muscle Fibers Longitudinally sectioned skeletal muscle fibers show cross- striations of alternating light and dark bands (Figure 10-7). “The dark bands ate called A bands (anisotropic or bireftin- gent in polarized light microscopy); the light bands are called | bands (isotropic, do not alter polarized light). In the TEM (Figure 10-7¢), each Iband is seen tobe bisected by a dark transverse line, the Z dise (Ger. zwischen, between). The repetitive functional subunit of the contractile apparatus, the sarcomere, extends from Z disc to Z disc (Figure 10-8) and {s about 25 jum long in resting muscle, “The sarcoplasm has little RER and contains primarily long cylindrical filament bundles, called myofibrils, running parallel to the long axis of the fiber (Figure 10-8a). Mitochondria and sarcoplasmic reticulum are found between the myofibrils, which have a diameter of 1 to 2 um. Myofbrils consist of an end-to- end repetitive arrangement of sarcomeres (Figure 10-88); the lateral registration of sarcomeres in adjacent myofibrils causes the entire muscle fiber to exhibit a characteristic pattern of transverse striations Sielotal Muscle 193 Salta muscle asco foer ‘An entire skeletal muscle Is enclosed within a thlek ayer of dense connective tissue caled the epimysium that is con- tinuous with fascia and the tendon binding muscle to bone, Large muscles contain several fascicles of muscle tissue, ‘each wrapped ina thin but dense connective tissue layer called the perimysium. Within fascicles individual muscle fibers (elongated multinuclear cells) are surrounded by a delicate connective tissue layer, the endomysium. ‘The A and I banding pattern in sarcomeres is due mainly to the regular arrangement of thick and thin myofilaments, composed of myosin and Feactin, respectively, organized within each myofibril ina symmetric pattern containing thou- sands of each filament type. “The thick myosin filaments are 1.6 pm long and 15 nm wide; they occupy the A band at the middle region of the sarcomere. Myosin is a large complex (~500 kDa) with, ‘O}9SnIN IE}9IHS « onssiL s}osnW Q T ¥3LavHo194 CHAPTER I0 = Muscle Tasue i ee i = io oS (2) Micrograph shows a oross section of striated muscle demonstrating connective issue and cell nucel. The endo rnysium (En) surounds individual muscle, and permysium (P) encloses a group of muscle tbers comprising a fascicle. A thick epinysium (E) surrounds the entire muscle. All three of these tissues contain collagen types | and Il reticulin). %200. HAE. (b) Adjacent section immunohistochemieally stained for laminin, which specifically stains the external laminae of muscle fers within te endoneurium, X400, immunoper oxidase. two identical heavy chains and two pairs of light chains Myosin heavy chains are thin, roditke motor proteins (150 rm long and 2-3 am thick) twisted together as myosin tails (Figure 10-9). Globular projections containing the four myosin light chains form a head at one end of each heavy chain. The myosin heads bind both actin, forming transient cxossbridges between the thick and thin filaments, and ATP, catalyzing energy release (actomyosin ATPase activity) Several hundred myosin molecules are arranged within each thick filament with overlapping rodlike portions and the globular heads directed toward either end (Figure 10-92). font ees The blood vessels were Injected with a dark plastic polymer before the muscle was collected an sectioned longitud- nally. rich network of capillaries in endomysium surround ing muscle fibers is revealed by this method. X200, Giemsa with polarize light. ‘The thin, helical actin filaments are each 1.0 wm long and 8 nm wide and run between the thick filaments. Each G-actin monomer contains a binding site for myosin, (Figure 10-9). Actin filaments are anchored perpendic- ularly on the Z disc by the actin-binding protein a-actinin and exhibit opposite polarity on cach side of this dise nr Tendons develop together with skeletal muscles anc join ‘muscles to the periosteum of tones. The collagen flrs ‘of a tendon (T) are continuous with those in the connective tissue layers around muscle fibers (M), forming a strong. Unit that allows muscle contraction to move the skeleton. X400. H&E.eer rare Longitudinal sections reveal the striations characteristic of ‘skeletal muscle. (a) Parts of three muscle fers are sepa- rated by very small amounts of endomysium. One fioroblast ‘nucleus (F) shown, Muscle nucle (N) are found against the sarcolemma. Along each fiber thousands of dark- ‘staining A bands alternate with lighter I bands. X200. H&E, (8) At higher magnification, each fiber can be seen to have three or four nyofions, nee with their stiations slightly ‘out of alignment with one another. Myofixils are cylindrical bundles of thick and thin myoflaments that fl most of each ‘muscle flor. The middle of each I band can be seen to hhave a darker Z line (or se). X500. Giems: {€) TEM showing the more electron-dense A bands bisected bya narrow, less electrorcdense region called the H zone {and in the I bands the presence of sarcoplasm with mito. chondria (M), glycogen granules, and small cistemae of 'SER around the Z line. X24,000, (Figure 10-76, with permission, trom Mikel H. Snow, Department of Cell and Neurobiology, Keck Schoo! of Mea cine at the University of Southern California, Los Angeles.) Sieleal Muscle 195 (Figure 10-80). Thin filaments are also tightly associated with two regulatory proteins (Figure 10-9): . 40-nm-long coil of two polypeptide chains located in the groove between the two twisted, actin strands. . ‘a complex of three subunits: THT, which at- taches to tropomyosin; TaC, which binds Ca; and Tal, which regulates the actin-myosin interaction, ‘Troponin complexes attach at specific sites regularly spaced along each tropomyosin molecule hands, each bisected by a Z disc, consist of the portions of the thin filaments that do not overlap the thick flaments (which is way I ands stain more lightly), An important acces- sory protein in I bands is titin (3700 kDa), the largest protein in the body, with scaffolding and elastic properties, which sup- ports the thick myofilaments and connects them to the Z disc (Figure 10-8). Another very large accessory protein, (600-900 kDa), binds each thin myofilament laterally, helps anchor them to a-actinin, and specifies the length of the actin polymers during myogenesis. ‘The A bands contain both thick filaments and the over- lapping portions of thin filaments, Close observation of the ‘A band shows the presence ofa lighter zone in its center, the HE zone, corresponding to a region with only the rodlike portions of the myosin molecule and no thin filaments (Figure 10-8c), Bisecting the H zone is the M line (Ger. Mitte, middle; Figure 10-8), containing a myosin-binding protein that holds the thick filaments in place, and ‘This enzyme catalyzes transfer of phosphate groups from phosphocreatine, a storage form of high-energy phosphate groups, to ADP, helping to supply ATP for muscle contraction, Despite the many proteins present in sarcomeres, myo- sin and actin together represent over half of the total protein. in striated muscle, The overlapping arrangement of thin and thick filaments within sarcomeres produces in TEM cross sec- sions hexagonal patterns of structures that were important in. determining the functions ofthe filaments and other proteins in the myofibril (Figures 10-8b and 10-8). Sarcoplasmic Reticulum & Transverse Tubule System In skeletal muscle fibers the smooth ER, or is specialized for Ca" sequestration. Depolariza- tion of the sarcoplasmic reticulum membrane, which causes release of calcium, is initiated at specialized motor nerve synapses on the sarcolemma, To trigger Ca’' release from sarcoplasmic reticulum throughout the fiber simultaneously and cause uniform contraction of all myofibrils, the sarco- lemma is folded into 2 system of or (Figures 10-102 and 10-11). These long fingerlike invagi- nations of the cell membrane penetrate deeply into the sar- coplasm and encircle every myofibril near the aligned A- and band boundaries of sarcomeres (Figures 10-105 and 10-11) uaievio S19SMIW IeI9I9HS = OnssL>PSOW Q T.Tee ere i Connecin Thin Thin. Thick = hike Tn ‘iamente (| band PA Abana ® I] izase Tae eee iT) we /-— sarcomere Thiniloment yy : ‘Thick iament ¥ 2dtenin dee — lara band leant [/_- sercormare ——4 parallel undies called myofibrils {b) Each myofiorl consists ofa long series of sarcomeres, Separated by Z discs andl containing thick and thin ‘laments ‘that overlap in certain regions. {€) Thin filaments are actin flaments with one end bound to ‘-aetlnin in the Z aise. Thick filaments are bundles of myosin, which span the entire A banc and are bound to proteins of the M line and to the Z dise across the I hands by a very large protein called ttn, which has spring {@) The molecular organization of the sarcomeres produces staining differences that cause the dark- and ligt staining bands seen by light microscopy and TEM. X28,000. {€) With the TEM an oblique section of myofbis includes both ‘A and I bands and shows hexagonal patterns that indicate the relationships between thin and thick myofllaments and other proteins, a shown in part b ofthis figure. Thin and thick fla ments ate arranged so that each myosin bundle contacts six ‘2ctin filaments. Large mitochonatia in cross-section and SER cisternae are seen between the myofibrils, X85,000.,Myofiba Myotlaments Myosin hoads Myosin molecule Sieleal Muscle 197 10-9 Molecules composing thin and thick fla Muscle fiver Heads feti-inaing ste | arp. anc ATPase-binding ste 2 Thiek flament Topemyosin Topenin—Cat-binding st Myesin-binding se Thin filament Myofaments, which include both thick and thn flaments, consist of contractile protein arrays bundled within myo‘ Adjacent to each side of every T tubule are expanded ter minal cisterns of the sarcoplasmic reticulum, In longitudinal ‘TEM sections, this complex of T tubule with two closely asso- ciated small cisterns of sarcoplasmic reticulum on each side is known as a trlad (Figures 10-10b and 10-11). After depo- larization of the sarcoplasmic reticulum membrane, calcium fons concentrated within these cisternae are released through. Ca channels in the membrane into cytoplasm surrounding the thick and thin filaments. Cat binds troponin and allows bridging between actin and myosin molecules. When the membrane depolarization ends, the sarcoplasmic reticulum pumps Ca back into the cisternae, ending contractile activity, “Together, the triad components make up a signaling apparatus for converting repeated cell membrane depolarizations into spikes of fre, eytoplasmic Ca* that trigger contraction. Mechanism of Contraction During contraction, neither the thick nor thin filaments change their length. Contraction results as the overlapping thin and thick filaments of each sarcomere slide past one another. (2) A thick myoflamemt contains 200500 molecules of ‘myosin. (b) A thin flarent contains Faetin, tropomyesin, and ‘troponin, Contraction is induced when an action potential arrives ata synapse, the neuromuscular junction (NMJ), and is transmit ted along the T tubules to the sarcoplasmic reticulum to trig- ger Ca release. Figure 10-1] summarizes the key molecular events in muscle contraction. In a resting muscle, the myosin heads cannot bind G-actin because the binding sites are blocked by the troponin- \ropomyosin complex on the F-actin filaments. Caleium ions released upon neural stimulation bind troponin, changing its shape and moving tropomyosin on the F-actin (o expose the myosin-binding active sites and allow erossbridges to form, [Binding actin produces a conformational change or pivot in the myosins, which pulls the thin filaments farther into the A band, toward the Z disc, Energy for the pivot and pulling of actin is provided by hydrolysis of ATP bound to the myosin heads, ater which myosin binds another ATP and detaches from actin, In the continued presence of Ca and ATP, these attach-pivot-detach events occur in a repeating cycle, each lasting about 50 milliseconds, which shortens the sarcomere and contracts the muscle (Figure 10-12). A single muscle con- traction results from hundreds of these cycles : i i i : i z= i198 cHAPTERI0. = Muscle Tasue ee ‘Transverse tubules are invaginations of the sarcolemma that penetrate deeply into the muscle fber around all myofirl {2) TEM cross section of fish muscle shows portions of 0 ‘bers and the endomysium (E) between them. Several tans- verse or T tubules (T) are shown, perpendicular to the fer surface, penetrating between myofibrils (M). X50,000. (b) Highermagnifcation TEM of skeletal muscle in longitudinal section shows four membranaus triads (Tt) cut ansversely near the Atband--banc junctions. Each Wiad consists of @ ‘When the neural impulse stops and levels of free ealeium diminish, tropomyosin again covers the myosin-binding sites ‘on actin and the filaments passively slide back and sarcomeres, return to their relaxed length. In the absence of ATR, the actin- myosin crossbridges become stable, which accounts for the rigidity of skeletal muscles (rigor mortis) that occurs as mito- chondrial activity stops after death, Innervation [Myelinated motor nerves branch out within the perimysium ‘connective tissue, where each nerve gives rise to several unmy- clinated terminal twigs that pass through endomysium and form synapses with individual muscle fibers. Schwann cells ‘enclose the small axon branches and cover their points of con- tact with the muscle cells (Figure 10-13); the external lamina of ‘the Schwann cell fuses with that of the sarcolemma. Each axo- ‘al branch forms a dilated termination situated within a trough ‘on the muscle cell surface. This synaptic structure is called the motor end plate (MEP), or NMJ (Figure 10-13). Within the axon terminal are mitochondria and numerous synaptic vesicles, the latter containing the neurotransmitter acetyl ‘choline, Between the axon and the muscle is a space, the syn- aptic cleft, Adjacent to the synaptic clef, the sarcolemma is Central transverse tubule (T) and two adjacent terminal stems (Te) extending trom the sarcoplasmic reticulum, CGentally located is the Z disc. Besides elements of the triad, sarcoplasm surrouncing the nyofirl alse contains dense. _gyeogen granules (@), ‘Components ofthe trad are responsible for the cyclic release of Ca’ from the cistemae and its sequestration again that occurs during muscle contraction and relaxation. The ‘association between SR cisternae and T tubules is shown siagrammatically in Figure 10-11, X80,000, thrown into numerous deep junctional folds, which provide for greater postsynaptic surface atea and more transmembrane acetylcholine receptors ‘When nerve action potential reaches the MEP, acetyl- choline is iberated from the axon terminal, difuses across the lef, and binds to its receptors in the folded sarcolemma, The acetylcholine receptor contains a nonselective cation chan- rel that opens upon neurotransmitter binding, allowing influx ‘of Na", depolarizing the sarcolemma, and producing the mus~ cle action potential. Acetylcholine quickly dissociates from its receptors, and all free neurotransmitter is removed from the synaptic cleft by the extracellular enzyme acetyicholines- terase, preventing prolonged contact of the transmitter with its receptors. As discussed with Figure 10-11, the action potential initi- atedat the MEP moves along the surface of the muscle cll and along T tubules that penetrate deeply into sarcoplasm. Attri- ads the depolarization signal triggers the release of Ca from terminal cisterns of the sarcoplasmic reticulum, initiating the contraction cycle, ‘An axon froma single motor neuron can form MEPs with, ‘one or many muscle fibers. Innervation of single muscle fibers by single motor neurons provides precise control of muscle activity and occurs, for example, in the extraocular muscles‘Siolta Muscle 299) DArene impulse wages release tACh om the syrase knob to ‘hesyrape clot ACh ons to [Ch receptor inthe motor en pte of he reuromazeular Juncton stat a muscle Impulee nt srclomma o muscle ton As the muscle impulse spreads ‘ule trom the sarcolemma Along tubules, calcium ins are feleased irom iorminal esternae Int the sarcopasm, pctv ses ‘locked Gren ive mpuse slope catum ions are elvey__ @Caleumions bs to woponnTopnin changes shape, moving ‘ravapored intone steps em. \oponyosin ene asin oeoue are ares onset mokeles topomyoan recovers acive ses and aren crtin Hamers nhoan Reade of thck ont atch o exposed para de back oth lad ae, Sete ster orm Sossoragee “ate ae Cael — in tien | examen + ‘@ myosin heads pivot, moving thn flaments toward the sarcomere center ATP binds myosin heads and is broken down info ADP and > [Myosin heade detach ‘rm hin laments and return to thee prepive poston. The repeating cycle of attach pivot detachrotun sis thick and tin flames past one another The sarcomere shorens and the muscle contraes. The eycle continues a lng a8 calcium ions remain bound to toporin to Keep acve sites exposed.200 cHAPTERI0 = Muscle Tasue 10-12 Sliding flaments and s Eo eee [ets atcomare [Retna earamere Zeisc Thick lament Zese Thin | Tntfanent | yg _Thnhament t Zdse tine Zdse 1 Relaxed sholetal muscle ne rity conracios » Fully contracted akeetal muscle Sacemere Diagrams and TEM micrographs show sarcomere shortening uring skeletal muscle contraction. (a) In the relaxed state the sarcomere, | band, and H zane are al their expanded length. ‘The springlike action of tin molecules, which span the | bang, Helps pul hin and thick laments past ane another in for eye movements, Larger muscles with coarser movements have motor axons that typically branch profusely and inner- vate 100 or more muscle fibers. In this case the single axon and all the muscle fibers in contact with its branches make up 4 motor unit, Individual striated muscle fibers do not show graded contraction—they contract either all the way or not a all, To vary the force of contraction, the fibers within a mus- dle fascicle da not all contract at the same time, With large muscles composed of many motor units, the fring ofa single -motor axon will generate tension proportional to the number of muscle fibers it innervates, Thus, the number of motor units and their variable size contol the intensity and precision of a ‘muscle contraction, Key features of skeletal muscle cells, connective tissue, ‘contraction, and innervation are summarized in Table 10-1. Zeiee y = > conttacton [Paty corrntes relaxed muscle. (b) During muscle contraction, the Z discs at the sarcomere boundaries are drawn closer together as they mave toward the ends of thick flaments inthe A aan Tin molecules are compressed during contraction, frente Myasthenia gravis is an autoimmune disorder that involves. circulating antibodies against proteins of acetylcholine receptors. Antibody binding to the antigenic sites inter {eres with acetylcholine activation oftheir receptors, lead ing to intermittent periods of skeletal muscle weakness. {ks the body attempts to correct the condition, junctional {olds of sarcolemma with affected receptors ate inter nalized, digested by lysosomes, and replaced by newly formed receptors. These receptors, however, are again, made unresponsive to acetylcholine by similar antibod. Jes, and the disease follows a progressive course. The ‘extraocular muscles of the eyes are commonly the first affected.Sieloal Muscle 201 10-13 The neuromuscular junction (NMJ). Betore it ter bundled in the nerve forms mary branches, each of whieh, forms a synapse witn a muscle fiber. (2) Siver staining can reveal the nerve bundle (NB), the terminal ‘axonal tgs, anc the motor end plates (MEP, also called neuro- ‘muscular Junctions or NMU) on stated muscle bers (S). X1200, (b) An SEM shows the branching ends of a motor axon, each covered by an extension of the last Schwann cell and expanded Muscle Spindles & Tendon Organs Striated muscles and myotendinous junctions contain sen- sory receptors acting a8 proprioceptors (L. proprius, one’s own + capio, to take), providing the central nervous sys- tem (CNS) with data ffom the musculoskeletal system. ‘terminally as an MEP embedded ina groove inthe external lamina of the muscle fbr. (€) Diagram of enclosed portion of the SEM incating key fee ‘ues of atypical MEP: synaptle vesicles of acetycholine (ACR). 2 ‘synaptic cle, and a postsynaptic membrane. This membrane, the sarcolemma, is highly folded to increase the number of ACh recep- tors atthe MEP Receptor bincing itiates muscle fer depolariza- ‘lon, which is caried tothe deeper myotonls by the T tubules. ‘Among the muscle fascicles are stretch detectors known as muscle spindles, approximately 2mm long and 0.1 mm wide (Eigure 10-14a), A muscle spindle is encapsulated by modi- fied perimysium, with concentric layers of flattened els, containing interstitial fluid and a few thin muscle fibers filled ‘O}9SnIN IE}9IHS « onssiL s}osnW Q T ¥3LavHo