10

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C H A P T E R
Muscle Tissue

SKELETAL MUSCLE 193 CARDIAC MUSCLE 207

Organization of a Skeletal Muscle 194 SMOOTH MUSCLE 208
Organization Within Muscle Fibers 194
REGENERATION OF MUSCLE TISSUE 213
Sarcoplasmic Reticulum & Transverse
Tubule System 197 SUMMARY OF KEY POINTS 213
Mechanism of Contraction 198 ASSESS YOUR KNOWLEDGE 214
Innervation 200
Muscle Spindles & Tendon Organs 203
Skeletal Muscle Fiber Types 205

M uscle 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. As in all cells, actin microfilaments
and associated proteins generate the forces necessary for the
cells is o%en 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. lemma, husk).

muscle contraction, which drives movement within organ

systems, of blood, and of the body as a whole. Essentially all › › MEDICAL APPLICATION
muscle cells are of mesodermal origin and differentiate by a The variation in diameter of muscle fibers depends on factors
gradual process of cell lengthening with abundant synthesis of such as the specific muscle, age, gender, nutritional status,
the myofibrillar proteins actin and myosin. and physical training of the individual. Exercise enlarges the
Three types of muscle tissue can be distinguished on skeletal musculature by stimulating formation of new myofi-
the basis of morphologic and functional characteristics brils and growth in the diameter of individual muscle fibers.
(Figure 10–1), with the structure of each adapted to its physi- This process, characterized by increased cell volume, is called
ologic role. hypertrophy (Gr. hyper, above + trophe, nourishment). Tis-
■ Skeletal muscle contains bundles of very long, multi- sue growth by an increase in the number of cells is termed
nucleated cells with cross-striations. Their contraction is hyperplasia (hyper + Gr. plasis, molding), which takes place
quick, forceful, and usually under voluntary control. very readily in smooth muscle, whose cells have not lost the
■ Cardiac muscle also has cross-striations and is com- capacity to divide by mitosis.
posed of elongated, o%en branched cells bound to one

› SKELETAL MUSCLE
another at structures called intercalated discs which
are unique to cardiac muscle. Contraction is involuntary,
vigorous, and rhythmic.
Skeletal (or striated) muscle consists of muscle fibers,
■ Smooth muscle consists of collections of fusiform
which are long, cylindrical multinucleated cells with diam-
cells which lack striations and have slow, involuntary
eters of 10-100 μm. During embryonic muscle development,
contractions.
mesenchymal myoblasts (L. myo, muscle) fuse, forming myo-
In all types of muscle, contraction is caused by the slid- tubes with many nuclei. Myotubes then further differentiate to
ing interaction of thick myosin filaments along thin actin fila- form striated muscle fibers (Figure 10–2). Elongated nuclei are
ments. The forces necessary for sliding are generated by other found peripherally just under the sarcolemma, a characteristic
proteins affecting the weak interactions in the bridges between nuclear location unique to skeletal muscle fibers/cells. A small
actin and myosin. population of reserve progenitor cells called muscle satellite
As with neurons, muscle specialists refer to certain mus- cells remains adjacent to most fibers of differentiated skeletal
cle cell organelles with special names. The cytoplasm of muscle muscle.

193
 194 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–1 Three types of muscle.

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Striations Connective Intercalated disc Glycogen

Nuclei Muscle fiber tissue Branching Striations Nucleus Nuclei Muscle cells

(a) Skeletal muscle (b) Cardiac muscle (c) Smooth muscle

Light micrographs of each type, accompanied by labeled draw- strong, involuntary contractions. (c) Smooth muscle is com-
ings. (a) Skeletal muscle is composed of large, elongated, multi- posed of grouped, fusiform cells with weak, involuntary contrac-
nucleated fibers that show strong, quick, voluntary contractions. tions. The density of intercellular packing seen reflects the small
(b) Cardiac muscle is composed of irregular branched cells amount of extracellular connective tissue present. ([a, b]: X200;
bound together longitudinally by intercalated discs and shows [c]: X300; All H&E)

Organization of a Skeletal Muscle Collagens in these connective tissue layers of muscle serve
to transmit the mechanical forces generated by the contract-
Thin layers of connective tissue surround and organize the
ing muscle cells/fibers; individual muscle fibers seldom extend
contractile fibers in all three types of muscle, and these layers
from one end of a muscle to the other.
are seen particularly well in skeletal muscle (Figures 10–3 and
All three layers plus the dense irregular connective tissue
10–4). The concentric organization given by these supportive
of the deep fascia, which overlies the epimysium, are continu-
layers resembles that in large peripheral nerves:
ous with the tough connective tissue of a tendon at myoten-
■ The epimysium, an external sheath of dense irregular dinous junctions which join the muscle to bone, skin, or
connective tissue, surrounds the entire muscle. Septa another muscle (Figures 10–3 and 10–4c). Ultrastructural
of this tissue extend inward, carrying the larger nerves, studies show that in these transitional regions, collagen fibers
blood vessels, and lymphatics of the muscle. from the tendon insert themselves among muscle fibers and
■ The perimysium is a thin connective tissue layer that associate directly with complex infoldings of sarcolemma.
immediately surrounds each bundle of muscle fibers
termed a fascicle (Figure 10–3). Each fascicle of muscle
fibers makes up a functional unit in which the fibers Organization Within Muscle Fibers
work together. Nerves, blood vessels, and lymphatics Longitudinally sectioned skeletal muscle fibers show striations
penetrate the perimysium to supply each fascicle. of alternating light and dark bands (Figure 10–6a). The sarco-
■ Within fascicles a very thin, delicate layer of reticular plasm is highly organized, containing primarily long cylindrical
fibers and scattered fibroblasts, the endomysium, sur- filament bundles called myofibrils that run parallel to the long
rounds the external lamina of individual muscle fibers. axis of the fiber (Figure 10–6b). The dark bands on the myofi-
In addition to nerve fibers, capillaries form a rich net- brils are called A bands (anisotropic or birefringent in polarized
work in the endomysium bringing O2 to the muscle light microscopy); the light bands are called I bands (isotropic,
fibers (Figure 10–5). do not alter polarized light). In the TEM (Figure 10–6c), each I
 Skeletal Muscle 195

FIGURE 10–2 Development of skeletal muscle. FIGURE 10–3 Organization of skeletal muscle.

C H A P T E R
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Myoblasts
Tendon
Myoblast

1 0
Satellite cell
fusion to form
myotubes
Deep fascia

Muscle Tissue ■ Skeletal Muscle

Epimysium
Skeletal muscle

Differentiation
Satellite cell
Muscle fiber

Artery
Vein Perimysium
Skeletal muscle begins to differentiate when mesenchymal Nerve
cells, called myoblasts, align and fuse together to make longer,
Fascicle
multinucleated tubes called myotubes. Myotubes synthesize
the proteins to make up myofilaments and gradually begin to
show cross-striations by light microscopy. Myotubes continue
differentiating to form functional myofilaments, and the nuclei
are displaced against the sarcolemma.
Part of the myoblast population does not fuse and differenti- Endomysium
ate but remains as a group of mesenchymal cells called muscle
satellite cells located on the external surface of muscle fibers
inside the developing external lamina. Satellite cells proliferate Muscle fiber
and produce new muscle fibers following muscle injury.

band is seen to be bisected by a dark transverse line, the Z disc

(Ger. zwischen, between). The repetitive functional subunit of the
contractile apparatus, the sarcomere, extends from Z disc to Z
disc (Figure 10–6c) and is about 2.5-μm long in resting muscle.
Mitochondria and sarcoplasmic reticulum are found An entire skeletal muscle is enclosed within a thick layer of
between the myofibrils, which typically have diameters of 1-2 dense connective tissue called the epimysium that is con-
μm. Myofibrils consist of an end-to-end repetitive arrange- tinuous with fascia and the tendon binding muscle to bone.
Large muscles contain several fascicles of muscle tissue, each
ment of sarcomeres (Figure 10–7); the lateral registration of
wrapped in a thin but dense connective tissue layer called the
sarcomeres in adjacent myofibrils causes the entire muscle perimysium. Within fascicles individual muscle fibers (elon-
fiber to exhibit a characteristic pattern of transverse striations. gated multinuclear cells) are surrounded by a delicate connec-
The A and I banding pattern in sarcomeres is due mainly tive tissue layer, the endomysium.
to the regular arrangement of thick and thin myofilaments,
composed of myosin and F-actin, respectively, organized
within each myofibril in a symmetric pattern containing thou-
sands of each filament type (Figure 10–7). bind both actin, forming transient crossbridges between the
The thick myosin filaments are 1.6-μm long and 15-nm thick and thin filaments, and ATP, catalyzing energy release
wide; they occupy the A band at the middle region of the sar- (actomyosin ATPase activity). Several hundred myosin
comere. Myosin is a large complex (~500 kDa) with two iden- molecules are arranged within each thick filament with over-
tical heavy chains and two pairs of light chains. Myosin heavy lapping rodlike portions and the globular heads directed
chains are thin, rodlike motor proteins (150-nm long and toward either end (Figure 10–7a).
2-3 nm thick) twisted together as myosin tails (Figure 10–7). The thin, helical actin filaments are each 1.0-μm long and
Globular projections containing the four myosin light chains 8-nm wide and run between the thick filaments. Each G-actin
form a head at one end of each heavy chain. The myosin heads monomer contains a binding site for myosin (Figure 10–7b).
 196 CHAPTER 10 ■ Muscle Tissue

P
FIGURE 10–4 Skeletal muscle. P a
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En
E

P
a b
b

M T
M T

M
M

M
C M
C

(a)b A cross section of striated muscle demonstrating all three layers of the muscle fibers, surrounded by endomysium. (X400;
of connective tissue and cell nuclei. The endomysium (En) sur- Immunoperoxidase)
rounds individual muscle, and perimysium (P) encloses a group (c) Longitudinal section of a myotendinous junction. Tendons
of muscle fibers comprising a fascicle. A thick epimysium (E) sur-
rounds Mthe entire muscle. All three of these tissues containTcolla- develop together with skeletal muscles and join muscles to the
periosteum of bones. The dense collagen fibers of a tendon (T) are
gen types I and III (reticulin). (X200; H&E) continuous with those in the three connective tissue layers around
(b) An adjacent section immunohistochemically stained muscle fibers (M), forming a strong unit that allows muscle con-
for laminin, which specifically stains the external laminae traction to move other structures. (X400; H&E)
M

FIGURE 10–5 Capillaries of skeletal muscle.

M
C

The blood vessels were injected with a dark plastic polymer

before the muscle was collected and sectioned longitudinally.
A rich network of capillaries in endomysium surrounding muscle
fibers is revealed by this method. (X200; Giemsa with polarized
light)
 Skeletal Muscle 197

The thin filaments have two tightly associated regulatory pro-

FIGURE 10–6 Striated skeletal muscle in
teins (Figure 10–7b):

C H A P T E R
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longitudinal section.
■ Tropomyosin, a 40-nm-long coil of two polypeptide
chains located in the groove between the two twisted
A actin strands
I ■ Troponin, a complex of three subunits: TnT, which
attaches to tropomyosin; TnC, which binds Ca2+; and
TnI, which regulates the actin-myosin interaction

1 0
F
Troponin complexes attach at specific sites regularly
spaced along each tropomyosin molecule.

Muscle Tissue ■ Skeletal Muscle

The organization of important myofibril components is
a N shown in Figure 10–8. I bands consist of the portions of the
thin filaments which do not overlap the thick filaments in the
A bands, which is why I bands stain more lightly than A bands.
Actin filaments are anchored perpendicularly on the Z disc
by the actin-binding protein α-actinin and exhibit opposite
polarity on each side of this disc (Figure 10–8c). An important
accessory protein in I bands is titin (3700 kDa), the largest
protein in the body, with scaffolding and elastic properties,
which supports the thick myofilaments and connects them
to the Z disc (Figure 10–8c). Another large accessory protein,
nebulin, binds each thin myofilament laterally, helps anchor
them to (-actinin, and specifies the length of the actin poly-
b mers during myogenesis.
The A bands contain both the thick filaments and the over-
I lapping portions of thin filaments. Close observation of the
A band shows the presence of a lighter zone in its center, the H
Z A Z zone, corresponding to a region with only the rodlike portions
of the myosin molecule and no thin filaments (Figure 10–8c).
M Bisecting the H zone is the M line (Ger. Mitte, middle;
M
Figure 10–8d), containing a myosin-binding protein myome-
H sin that holds the thick filaments in place, and creatine kinase.
This enzyme catalyzes transfer of phosphate groups from phos-
c
phocreatine, a storage form of high-energy phosphate groups,
to ADP, helping to supply ATP for muscle contraction.
Longitudinal sections reveal the striations characteristic of skel- Despite the many proteins present in sarcomeres, myo-
etal muscle. sin and actin together represent over half of the total protein
(a) Parts of three muscle fibers are separated by very thin endo- in striated muscle. The overlapping arrangement of thin and
mysium that includes one fibroblast nucleus (F). Muscle nuclei thick filaments within sarcomeres produces in TEM cross sec-
(N) are found against the sarcolemma. Along each fiber thou- tions hexagonal patterns of structures which were important
sands of dark-staining A bands alternate with lighter I bands. in determining the functions of the filaments and other pro-
(X200; H&E)
teins in the myofibril (Figures 10–8b and 10–8e).
(b) At higher magnification, each fiber can be seen to have three or
four myofibrils, here with their striations slightly out of alignment
with one another. Myofibrils are cylindrical bundles of thick and thin Sarcoplasmic Reticulum & Transverse Tubule
myofilaments which fill most of each muscle fiber. (X500; Giemsa) System
(c) TEM showing one contractile unit (sarcomere) in the long
series that comprises a myofibril. In its middle is an electron-
In skeletal muscle fibers the membranous smooth ER, called
dense A band bisected by a narrow, less dense region called here sarcoplasmic reticulum, contains pumps and other
the H zone. On each side of the A band are the lighter-stained I proteins for Ca2+ sequestration and surrounds the myofi-
bands, each bisected by a dense Z disc which marks one end of brils (Figure 10–9). Calcium release from cisternae of the
the sarcomere. Mitochondria (M), glycogen granules, and small sarcoplasmic reticulum through voltage-gated Ca2+ chan-
cisternae of SER occur around the Z disc. (X24,000)
(Figure 10–6c, used with permission from Mikel H. Snow,
nels is triggered by membrane depolarization produced by
Department of Cell and Neurobiology, Keck School of Medicine at a motor nerve.
the University of Southern California, Los Angeles.) To trigger Ca2+ release from sarcoplasmic reticulum through-
out the muscle fiber simultaneously and produce uniform
 198 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–7 Molecules composing thin and thick filaments.

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Muscle fiber
Myofibril

Myofilaments Myosin molecule

Heads
Tail Actin-binding site
ATP- and ATPase-binding site

Myosin heads

a Thick filament

Tropomyosin Troponin Ca2+-binding site

G-actin F-actin Myosin-binding site

b Thin filament

Myofilaments, which include both thick and thin filaments, consist myofilament contains 200-500 molecules of myosin. (b) A thin fila-
of contractile protein arrays bundled within myofibrils. (a) A thick ment contains F-actin, tropomyosin, and troponin.

contraction of all myofibrils, the sarcolemma has tubular overlapping thin and thick filaments of each sarcomere slide
infoldings called transverse or T-tubules (Figures 10–9 past one another.
and 10–10). These long fingerlike invaginations of the cell Contraction is induced when an action potential arrives
membrane penetrate deeply into the sarcoplasm and encircle at a synapse, the neuromuscular junction (NMJ), and is
each myofibril near the aligned A- and I-band boundaries of transmitted along the T-tubules to terminal cisternae of the
sarcomeres. sarcoplasmic reticulum to trigger Ca2+ release. In a resting
Adjacent to each T-tubule are expanded terminal cister- muscle, the myosin heads cannot bind actin because the bind-
nae of sarcoplasmic reticulum. In longitudinal TEM sections, ing sites are blocked by the troponin-tropomyosin complex
this complex of a T-tubule with two terminal cisternae is called on the F-actin filaments. Calcium ions released upon neural
a triad (Figures 10–9 and 10–10). The triad complex allows stimulation bind troponin, changing its shape and moving
depolarization of the sarcolemma in a T-tubule to affect the tropomyosin on the F-actin to expose the myosin-binding
sarcoplasmic reticulum and trigger release of Ca2+ ions into active sites and allow crossbridges to form. Binding actin pro-
cytoplasm around the thick and thin filaments, which initiates duces a conformational change or pivot in the myosins, which
contraction of sarcomeres. pulls the thin filaments farther into the A band, toward the Z
disc (Figure 10–11).
Energy for the myosin head pivot that pulls actin is pro-
Mechanism of Contraction vided by hydrolysis of ATP bound to the myosin heads, a%er
Figure 10–11 summarizes the key molecular events of mus- which myosin binds another ATP and detaches from actin.
cle contraction. During this process neither the thick nor the In the continued presence of Ca2+ and ATP, these attach-
thin filaments change their length. Contraction occurs as the pivot-detach events occur in a repeating cycle, each lasting
 Skeletal Muscle 199

FIGURE 10–8 Structure of a myofibril: A series of sarcomeres.

C H A P T E R
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Connectin Titin Thin Thick Thick Thin

filaments filament filament filament filament filament

1 0
I band Z disc I band M line H zone A band

Muscle Tissue ■ Skeletal Muscle

b
A band
Myofibrils
Z disc M line Z disc

H zone

Sarcomere

a
A

Sarcomere
Thin filament M line

H zone

Thick filament e
Z disc Titin Z disc
I band A band I band
c
Sarcomere

M line
Z disc Z disc
H zone
d I band A band I band

(a) The diagram shows that each muscle fiber contains several par- (d) The molecular organization of the sarcomeres produces stain-
allel bundles called myofibrils. ing differences which cause the dark- and light-staining bands
(b) Each myofibril consists of a long series of sarcomeres, separated seen by light microscopy and TEM. (X28,000)
by Z discs and containing thick and thin filaments which overlap in (e) With the TEM an oblique section of myofibrils includes both
certain regions. A and I bands and shows hexagonal patterns that indicate the
(c) Thin filaments are actin filaments with one end bound to relationships between thin and thick myofilaments and other pro-
α-actinin in the Z disc. Thick filaments are bundles of myosin, teins, as shown in part b of this figure. Thin and thick filaments are
which span the entire A band and are bound to proteins of the arranged so that each myosin bundle contacts six actin filaments.
M line and to the Z disc across the I bands by a very large protein Large mitochondria in cross section and SER cisternae are seen
called titin, which has springlike domains. between the myofibrils. (X45,000)
 200 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–9 Organization of a skeletal muscle fiber.

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Triad
T-tubule
Terminal
cisterna

Sarcoplasmic
Muscle reticulum

Fascicle
Sarcoplasmic Triad
Muscle fiber reticulum (SR)
T-tubule Terminal
cisternae of SR

Sarcolemma

Nucleus

Myofibrils

Sarcomere

Thin & thick

Myofilaments

Nucleus
Openings into
T-tubules Sarcoplasm
Nucleus Mitochondrion

Skeletal muscle fibers are composed mainly of myofibrils. Each terminal cisternae of the sarcoplasmic reticulum. A T-tubule and its
myofibril extends the length of the fiber and is surrounded by parts two associated terminal cisterna comprise a “triad” of small spaces
of the sarcoplasmic reticulum. The sarcolemma has deep invagina- along the surface of the myofibrils.
tions called T-tubules, each of which becomes associated with two

about 50 milliseconds, which rapidly shorten the sarcomere branches and cover their points of contact with the muscle
and contract the muscle (Figures 10–11 and 10–12). A single cells (Figure 10–13); the external lamina of the Schwann cell
muscle contraction results from hundreds of these cycles. fuses with that of the sarcolemma. Each axonal branch forms a
When the neural impulse stops and levels of free Ca2+ dilated termination situated within a trough on the muscle cell
ions diminish, tropomyosin again covers the myosin-bind- surface, which are part of the synapses termed the neuromus-
ing sites on actin and the filaments passively slide back and cular junctions, or motor end plates (MEPs) (Figure 10–13).
sarcomeres return to their relaxed length (Figure 10–11). In As in all synapses the axon terminal contains mitochondria
the absence of ATP, the actin-myosin crossbridges become and numerous synaptic vesicles; here the vesicles contain the
stable, which accounts for the rigidity of skeletal muscles neurotransmitter acetylcholine. Between the axon and the
(rigor mortis) that occurs as mitochondrial activity stops muscle is the synaptic cleft. Adjacent to the synaptic cle%, the
a%er death. sarcolemma is thrown into numerous deep junctional folds,
which provide for greater postsynaptic surface area and more
transmembrane acetylcholine receptors.
Innervation When a nerve action potential reaches the MEP, acetyl-
Myelinated motor nerves branch out within the perimysium, choline is liberated from the axon terminal, diffuses across the
where each nerve gives rise to several unmyelinated terminal cle%, and binds to its receptors in the folded sarcolemma. The
twigs that pass through endomysium and form synapses with acetylcholine receptor contains a nonselective cation chan-
individual muscle fibers. Schwann cells enclose the small axon nel that opens upon neurotransmitter binding, allowing influx
 Skeletal Muscle 201

FIGURE 10–10 Transverse tubule system and triads.

C H A P T E R
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Tr
G Tr
T M

1 0
TC T TC
I Z I
A

Muscle Tissue ■ Skeletal Muscle

A
E
T Tr
G Tr

M
a b

Transverse tubules are invaginations of the sarcolemma that pen- transverse tubule (T) and two adjacent terminal cisterns (TC)
etrate deeply into the muscle fiber around all myofibrils. extending from the sarcoplasmic reticulum. Centrally located is the
(a) TEM cross section of fish muscle shows portions of two fibers Z disc. Besides elements of the triad, sarcoplasm surrounding the
and the endomysium (E) between them. Several transverse or myofibril also contains dense glycogen granules (G).
T-tubules (T) are shown, perpendicular to the fiber surface, pen- Components of the triad are responsible for the cyclic release
etrating between myofibrils (M). (X50,000) of Ca2+ from the cisternae and its sequestration again which occurs
during muscle contraction and relaxation. The association between
(b) Higher-magnification TEM of skeletal muscle in longitudinal SR cisternae and T-tubules is shown diagrammatically in Figure
section shows four membranous triads (Tr) cut transversely near 10–11. (X90,000)
the A-band–I-band junctions. Each triad consists of a central

of cations, depolarizing the sarcolemma, and producing the muscles composed of many motor units, the firing of a single
muscle action potential. Acetylcholine quickly dissociates motor axon will generate tension proportional to the number
from its receptors, and free neurotransmitter is removed from of muscle fibers it innervates. Thus, the number of motor units
the synaptic cle% by the extracellular enzyme acetylcholines- and their variable size control the intensity and precision of a
terase, preventing prolonged contact of the transmitter with muscle contraction.
its receptors. Key features of skeletal muscle cells, connective tissue,
As discussed with Figure 10–11, the muscle action poten- contraction, and innervation are summarized in Table 10–1.
tial moves along the sarcolemma and along T-tubules which
penetrate deeply into sarcoplasm. At triads the depolarization
signal triggers the release of Ca2+ from terminal cisterns of the › › MEDICAL APPLICATION
sarcoplasmic reticulum, initiating the contraction cycle. Myasthenia gravis is an autoimmune disorder that involves
An axon from a single motor neuron can form MEPs with circulating antibodies against proteins of acetylcholine
one or many muscle fibers. Innervation of single muscle fibers receptors. Antibody binding to the antigenic sites interferes
by single motor neurons provides precise control of muscle with acetylcholine activation of their receptors, leading to
activity and occurs, for example, in the extraocular muscles intermittent periods of skeletal muscle weakness. As the
for eye movements. Larger muscles with coarser movements body attempts to correct the condition, junctional folds
have motor axons that typically branch profusely and inner- of sarcolemma with affected receptors are internalized,
vate 100 or more muscle fibers. In this case the single axon digested by lysosomes, and replaced by newly formed recep-
and all the muscle fibers in contact with its branches make up tors. These receptors, however, are again made unresponsive
a motor unit. Individual striated muscle fibers do not show to acetylcholine by similar antibodies, and the disease follows
graded contraction—they contract either all the way or not at a progressive course. The extraocular muscles of the eyes are
all. To vary the force of contraction, the fibers within a mus- commonly the first affected.
cle fascicle do not all contract at the same time. With large
 202 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–11 Events of muscle contraction.

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Synaptic knob 1 A nerve impulse triggers release

of ACh from the synaptic knob into
Sarcolemma the synaptic cleft. ACh binds to
Synaptic vesicles ACh receptors in the motor end
plate of the neuromuscular
Neuromuscular Synaptic cleft Myofibril junction, initiating a muscle
junction 1
impulse in the sarcolemma of the
Muscle muscle fiber.
impulse
ACh
Motor end
ACh receptor plate
2 As the muscle impulse spreads
quickly from the sarcolemma
2
along T tubules, calcium ions are
Sarcoplasmic reticulum released from terminal cisternae
into the sarcoplasm.
Terminal cisternae
T-tubule
Calcium

Actin Active site

Troponin Tropomyosin Calcium
Active sites
blocked

Crossbridge

5 When the impulse stops, calcium ions are actively 3 Calcium ions bind to troponin. Troponin changes shape, moving
transported into the sarcoplasmic reticulum, tropomyosin on the actin to expose active sites on actin molecules
tropomyosin re-covers active sites, and filaments of thin filaments. Myosin heads of thick filaments attach to exposed
passively slide back to their relaxed state. active sites to form crossbridges.

Active site
Calcium

Thin filament

ATP ADP + P
Thick filament

4 Myosin heads pivot, moving thin filaments toward the sarcomere

center. ATP binds myosin heads and is broken down into ADP and P.
Myosin heads detach from thin filaments and return to their prepivot
position. The repeating cycle of attach-pivot-detach-return slides
thick and thin filaments past one another. The sarcomere shortens
and the muscle contracts. The cycle continues as long as calcium
ions remain bound to troponin to keep active sites exposed.
 Skeletal Muscle 203

FIGURE 10–12 Sliding filaments and sarcomere shortening in contraction.

C H A P T E R
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Relaxed sarcomere Relaxed sarcomere

Z disc Thick filament Z disc
Titin Thin filament Thin filament
M line
Z disc Z disc
M line

1 0
Muscle Tissue ■ Skeletal Muscle
H zone H zone
I band A band I band I band A band I band

a Relaxed skeletal muscle

Contraction Contraction

M line
Z disc Z disc
Z disc Z disc
M line

A band A band
Fully contracted Fully contracted
sarcomere sarcomere
b Fully contracted skeletal muscle

Diagrams and TEM micrographs show sarcomere shortening (b) During muscle contraction, the Z discs at the sarcomere bound-
during skeletal muscle contraction. (a) In the relaxed state the aries are drawn closer together as they move toward the ends of
sarcomere, I band, and H zone are at their expanded length. The thick filaments in the A band. Titin molecules are compressed dur-
springlike action of titin molecules, which span the I band, helps ing contraction.
pull thin and thick filaments past one another in relaxed muscle.

Muscle Spindles & Tendon Organs nerves relay this information to the spinal cord. Different
types of sensory and intrafusal fibers mediate reflexes of vary-
Striated muscles and myotendinous junctions contain sensory
receptors acting as proprioceptors (L. proprius, one’s own + ing complexity to help maintain posture and to regulate the
capio, to take), providing the central nervous system (CNS) activity of opposing muscle groups involved in motor activi-
with data from the musculoskeletal system. Among the mus- ties such as walking.
cle fascicles are stretch detectors known as muscle spindles, A similar role is played by Golgi tendon organs, much
approximately 2-mm long and 0.1-mm wide (Figure 10–14a). smaller encapsulated structures that enclose sensory axons
A muscle spindle is encapsulated by modified perimysium, penetrating among the collagen bundles at the myotendinous
with concentric layers of flattened cells, containing intersti- junction (Figure 10–14a). Tendon organs detect changes in
tial fluid and a few thin muscle fibers filled with nuclei and tension within tendons produced by muscle contraction and
called intrafusal fibers (Figure 10–14). Several sensory nerve act to inhibit motor nerve activity if tension becomes exces-
axons penetrate each muscle spindle and wrap around indi- sive. Because both of these proprioceptors detect increases in
vidual intrafusal fibers. Changes in length (distension) of the tension, they help regulate the amount of effort required to
surrounding (extrafusal) muscle fibers caused by body move- perform movements that call for variable amounts of muscu-
ments are detected by the muscle spindles and the sensory lar force.
 204 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–13 The neuromuscular junction (NMJ).

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NB
MEP

MEP

S
MEP

Axon from motor nerve

Myelin
Axon terminal
Schwann cell
Synaptic vesicles
(containing ACh)
Active zone

Sarcolemma Synaptic
cleft

Junctional
Nucleus of muscle fiber Region of folds
sarcolemma
with ACh receptors
b c

Before it terminates in a skeletal muscle, each motor axon bundled terminally as an MEP embedded in a groove in the external lamina
in the nerve forms many branches, each of which forms a synapse of the muscle fiber.
with a muscle fiber. (c) Diagram of enclosed portion of the SEM indicating key features
(a) Silver staining can reveal the nerve bundle (NB), the terminal of a typical MEP: synaptic vesicles of acetylcholine (ACh), a synaptic
axonal twigs, and the motor end plates (MEPs, also called neuro- cleft, and a postsynaptic membrane. This membrane, the sarco-
muscular junctions or NMJ) on striated muscle fibers (S). (X1200) lemma, is highly folded to increase the number of ACh receptors
(b) An SEM shows the branching ends of a motor axon, each at the MEP. Receptor binding initiates muscle fiber depolarization,
covered by an extension of the last Schwann cell and expanded which is carried to the deeper myofibrils by the T-tubules.
 Skeletal Muscle 205

TABLE 10–1 Important comparisons of the three types of muscle.

C H A P T E R
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Skeletal Muscle Cardiac Muscle Smooth Muscle

1 0
Muscle Tissue ■ Skeletal Muscle
Fibers Single multinucleated cells Aligned cells in branching Single small, closely packed fusiform
arrangement cells
Cell/fiber shape and Cylindrical, 10-100 μm diameter, Cylindrical, 10-20 μm diameter, Fusiform, diameter 0.2-10 μm, length
size many cm long 50-100 μm long 50-200 μm
Striations Present Present Absent
Location of nuclei Peripheral, adjacent to sarcolemma Central Central, at widest part of cell
T tubules Center of triads at A-I junctions In dyads at Z discs Absent; caveolae may be
functionally similar
Sarcoplasmic Well-developed, with two terminal Less well-developed, one small Irregular smooth ER without
reticulum (SR) cisterns per sarcomere in triads with terminal cistern per sarcomere in distinctive organization
T tubule dyad with T tubule
Special structural Very well-organized sarcomeres, SR, Intercalated discs joining cell, with Gap junctions, caveolae, dense
features and transverse tubule system many adherent and gap junctions bodies
Control of Troponin C binds Ca2+, moving Similar to that of skeletal muscle Actin-myosin binding occurs with
contraction tropomyosin and exposing actin for myosin phosphorylation by MLCK
myosin binding triggered when calmodulin binds
Ca2+
Connective tissue Endomysium, perimysium, and Endomysium; subendocardial and Endomysium and less-organized CT
organization epimysium subpericardial CT layers sheaths
Major locations Skeletal muscles, tongue, Heart Blood vessels, digestive and
diaphragm, eyes, and upper respiratory tracts, uterus, bladder,
esophagus and other organs
Key function Voluntary movements Automatic (involuntary) pumping Involuntary movements
of blood
Efferent innervation Motor Autonomic Autonomic
Contractions All-or-none, triggered at motor end All-or-none, intrinsic (beginning at Partial, slow, often spontaneous,
plates nodes of conducting fibers) wavelike and rhythmic
Cell response to Hypertrophy (increase in fiber size) Hypertrophy Hypertrophy and hyperplasia
increased load (increase in cell/fiber number)
Capacity for Limited, involving satellite cells Very poor Good, involving mitotic activity of
regeneration mainly muscle cells

Skeletal Muscle Fiber Types

› › MEDICAL APPLICATION
Skeletal muscles such as those that move the eyes and eyelids
Dystrophin is a large actin-binding protein located just
need to contract rapidly, while others such as those for bodily
inside the sarcolemma of skeletal muscle fibers, which
posture must maintain tension for longer periods while resist-
is involved in the functional organization of myofibrils.
ing fatigue. These metabolic differences are possible because of
Research on Duchenne muscular dystrophy revealed that
varied expression in muscle fibers of contractile or regulatory
mutations of the dystrophin gene can lead to defective link-
protein isoforms and other factors affecting oxygen delivery
ages between the cytoskeleton and the extracellular matrix
and use. Different types of fibers can be identified on the basis
(ECM). Muscle contractions can disrupt these weak linkages,
of (1) their maximal rate of contraction (fast or slow fibers)
causing the atrophy of muscle fibers typical of this disease.
and (2) their major pathway for ATP synthesis (oxidative
 206 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–14 Sensory receptors associated with skeletal muscle.

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SC
MA MF

MF MF
Capsule MF

Muscle spindle
SC
Intrafusal
muscle
fibers

Stretch C
receptor b
Afferent
nerve
fibers
Extrafusal (a) The diagram shows both a muscle spindle and a tendon
muscle organ. Muscle spindles have afferent sensory and efferent
fiber motor nerve fibers associated with the intrafusal fibers, which
are modified muscle fibers. The size of the spindle is exagger-
ated relative to the extrafusal fibers to show better the nuclei
packed in the intrafusal fibers. Both types of sensory receptors
provide the CNS with information concerning degrees of stretch
and tension within the musculoskeletal system.
(b) A TEM cross section near the end of a muscle spindle shows
the capsule (C), lightly myelinated axons (MA) of a sensory
Golgi tendon nerve, and the intrafusal muscle fibers (MF). These thin fibers
organ differ from the ordinary skeletal muscle fibers in having very
Tendon few myofibrils. Their many nuclei can either be closely aligned
(nuclear chain fibers) or piled in a central dilation (nuclear bag
a fibers). Muscle satellite cells (SC) are also present within the
external lamina of the intrafusal fibers. (X3600)

phosphorylation or glycolysis). Fast versus slow rates of fiber ■ Fast glycolytic fibers are specialized for rapid, short-
contraction are due largely to myosin isoforms with different term contraction, having few mitochondria or capillar-
maximal rates of ATP hydrolysis. ies and depending largely on anaerobic metabolism of
Histochemical staining is used to identify fibers with dif- glucose derived from stored glycogen, features which
fering amounts of “fast” and “slow” ATPases (Figure 10–15). make such fibers appear white. Rapid contractions lead
Other histological features reflecting metabolic differences to rapid fatigue as lactic acid produced by glycolysis
among muscle fibers include the density of surrounding capil- accumulates.
laries, the number of mitochondria, and levels of glycogen and ■ Fast oxidative-glycolytic fibers have physiological and
myoglobin, a globular sarcoplasmic protein similar to hemo- histological features intermediate between those of the
globin which contains iron atoms and allows for O2 storage. other two types.
Each of these features exists as a continuum in skeletal
Table 10–2 summarizes these and other characteristics of
muscle fibers, but fiber diversity is divided into three major
the three skeletal muscle fiber types. The metabolic type of each
types:
fiber is determined by the rate of impulse conduction along its
■ Slow oxidative muscle fibers are adapted for slow con- motor nerve supply, so that all fibers of a motor unit are similar.
tractions over long periods without fatigue, having many Most skeletal muscles receive motor input from multiple nerves
mitochondria, many surrounding capillaries, and much and contain a mixture of fiber types (Figure 10–15). Determin-
myoglobin, all features that make fresh tissue rich in ing the fiber types in needle biopsies of skeletal muscle helps
these fibers dark or red in color. in the diagnosis of specific myopathies (myo + Gr. pathos,
 Cardiac Muscle 207

FIGURE 10–15 Skeletal muscle fiber types. › CARDIAC MUSCLE

C H A P T E R
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During embryonic development mesenchymal cells around

the primitive heart tube align into chainlike arrays. Rather
than fusing into multinucleated cells/fibers as in developing
skeletal muscle fibers, cardiac muscle cells form complex
junctions between interdigitating processes (Figure 10–16).
Cells within one fiber o%en branch and join with cells in adja-

1 0
cent fibers. Consequently, the heart consists of tightly knit
bundles of cells, interwoven in spiraling layers that provide for
a characteristic wave of contraction that resembles wringing

Muscle Tissue ■ Cardiac Muscle

out of the heart ventricles.
Mature cardiac muscle cells are 15-30 μm in diameter and
85-120 μm long, with a striated banding pattern comparable to
that of skeletal muscle. Unlike skeletal muscle, however, each
cardiac muscle cell usually has only one nucleus and is cen-
trally located. Surrounding the muscle cells is a delicate sheath
SO of endomysium with a rich capillary network. A thicker peri-
mysium separates bundles and layers of muscle fibers and in
SO specific areas (described in Chapter 11) forms larger masses
of fibrous connective tissue comprising the “cardiac skeleton.”
SO A unique characteristic of cardiac muscle is the presence
of transverse lines that cross the fibers at irregular intervals
where the myocardial cells join. These intercalated discs
represent the interfaces between adjacent cells and consist
FG SO of many junctional complexes (Figure 10–16). Transverse
FG regions of these irregular, steplike discs are composed of
many desmosomes and fascia adherens junctions, which
FG together provide strong intercellular adhesion during the cells’
constant contractile activity. The less abundant, longitudinally
FOG
oriented regions of each intercalated disc run parallel to the
myofibrils and are filled with gap junctions which provide
ionic continuity between the cells. These regions serve as “elec-
trical synapses,” promoting rapid impulse conduction through
FOG many cardiac muscle cells simultaneously and contraction of
FOG many adjacent cells as a unit.
The structure and function of the contractile apparatus
in cardiac muscle cells are essentially the same as in skeletal
muscle (Figure 10–17). Mitochondria occupy up to 40% of
the cell volume, higher than in slow oxidative skeletal muscle
Cross section of a skeletal muscle stained histochemically for fibers. Fatty acids, the major fuel of the heart, are stored as tri-
myosin ATPase at acidic pH, which reveals activity of the “slow” glycerides in small lipid droplets. Glycogen granules as well as
ATPase and shows the distribution of the three main fiber perinuclear lipofuscin pigment granules may also be present.
types. Slow oxidative (SO) or type I fibers have high levels of
acidic ATPase activity and stain the darkest. Fast glycolytic (FG)
Muscle of the heart ventricles is much thicker than that
or type IIb fibers stain the lightest. Fast oxidative-glycolytic of the atria, reflecting its role in pumping blood through the
(FOG) or type IIa fibers are intermediate between the other cardiovascular system. T-tubules in ventricular muscle fibers
two types (X40). ATPase histochemistry of unfixed, cryostat are well-developed, with large lumens and penetrate the sarco-
section, pH 4.2. plasm in the vicinity of the myofibrils’ Z discs. In atrial muscle
T-tubules are much smaller or entirely absent. Sarcoplasmic
reticulum is less well-organized in cardiac compared to skel-
etal muscle fibers. The junctions between its terminal cisterns
and T-tubules typically involve only one structure of each
suffering), motor neuron diseases, and other causes of muscle type, forming profiles called dyads rather than triads in TEM
atrophy. Different fiber types also exist in cardiac muscle at sections. Components of this cardiac muscle transverse tubule
various locations within the heart and in smooth muscle of dif- system have the same basic functions as their counterparts in
ferent organs. skeletal muscle fibers.
 208 CHAPTER 10 ■ Muscle Tissue

TABLE 10–2 Major characteristics of skeletal muscle fiber types.

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Fast, Oxidative-Glycolytic Fast, Glycolytic

Slow, Oxidative Fibers (Type I) Fibers (Type IIa) Fibers (Type IIb)

Mitochondria Numerous Numerous Sparse

Capillaries Numerous Numerous Sparse
Fiber diameter Small Intermediate Large
Size of motor unit Small Intermediate Large
Myoglobin content High (red fibers) High (red fibers) Low (white fibers)
Glycogen content Low Intermediate High
Major source of ATP Oxidative phosphorylation Oxidative phosphorylation Anaerobic glycolysis
Glycolytic enzyme activity Low Intermediate High
Rate of fatigue Slow Intermediate Fast
Myosin-ATPase activity Low High High
Speed of contraction Slow Fast Fast
Typical major locations Postural muscles of back Major muscles of legs Extraocular muscles

Cardiac muscle fiber contraction is intrinsic and sponta-

neous, as evidenced by the continued contraction of the cells
› SMOOTH MUSCLE
in tissue culture. Impulses for the rhythmic contraction (or Smooth muscle is specialized for slow, steady contraction
heartbeat) are initiated, regulated, and coordinated locally by under the influence of autonomic nerves and various hor-
nodes of unique myocardial fibers specialized for impulse gen- mones. This type of muscle is a major component of blood
eration and conduction, which are discussed in Chapter 11. vessels and of the digestive, respiratory, urinary, and repro-
As with skeletal muscle fibers, contraction of individual ductive tracts and their associated organs. Fibers of smooth
myocardial fibers is all-or-none. The rate of contraction is mod- muscle (also called visceral muscle) are elongated, tapering,
ified by autonomic innervation at the nodes of conducting cells, and unstriated cells, each of which is enclosed by an external
with the sympathetic nerve supply accelerating and the para- lamina and a network of type I and type III collagen fibers
sympathetic supply decreasing the frequency of the impulses. comprising the endomysium (Figure 10–18).
Secretory granules about 0.2-0.3 μm in diameter are found Smooth muscle cells range in length from 20 μm in small
near atrial muscle nuclei and are associated with small Golgi com- blood vessels to 500 μm in the pregnant uterus. At each cell’s
plexes (Figure 10–17b). These granules release the peptide hor- central, broadest part, where its diameter is 5-10 μm, is a sin-
mone atrial natriuretic factor (ANF) which acts on target cells in gle elongated nucleus. The cells stain uniformly along their
the kidney to affect Na+ excretion and water balance. The contrac- lengths, and close packing is achieved with the narrow ends
tile cells of the heart’s atria thus also serve an endocrine function. of each cell adjacent to the broad parts of neighboring cells.
Key features of cardiac muscle cells, with comparisons to With this arrangement cross sections of smooth muscle show
those of skeletal muscle, are summarized in Table 10–1. a range of cell diameters, with only the largest profiles contain-
ing a nucleus (Figures 10–18 and 10–19a). All cells are linked
by numerous gap junctions. The borders of the cell become
› › MEDICAL APPLICATION scalloped when smooth muscle contracts and the nucleus
becomes distorted (Figure 10–20). Concentrated near the
The most common injury sustained by cardiac muscle is that
nucleus are mitochondria, polyribosomes, RER, and vesicles
due to ischemia, or tissue damage due to lack of oxygen
of a Golgi apparatus. At the smooth muscle cell surface are
when coronary arteries are occluded by heart disease. Lack-
numerous small plasmalemma invaginations resembling
ing muscle satellite cells, adult mammalian cardiac muscle
caveolae, which in these cells compartmentalize various sig-
has little potential to regenerate after injury. However, certain
naling components.
fish and amphibians, as well as newborn mice, do form new
The fibers have rudimentary sarcoplasmic reticulum, but
muscle when the heart is partially removed, despite the lack
lack T-tubules; their function is unnecessary in these smaller,
of satellite cells. Research on the possibility of mammalian
tapering cells with many gap junctions. Caveolae of smooth
heart muscle regeneration builds on work with the animal
muscle cells contain the major ion channels that control Ca2+
models, focusing primarily on the potential of mesenchymal
release from sarcoplasmic cisternae at myofibrils that initiates
stem cells to form new, site-specific muscle.
contraction. The characteristic contractile activity of smooth
 Smooth Muscle 209

FIGURE 10–16 Cardiac muscle.

C H A P T E R
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Openings of
(a) Intercalated disc transverse tubules Intercalated disc

Desmosome

1 0
Muscle Tissue ■ Smooth Muscle
Gap junction

Cardiac muscle cell

Sarcolemma

Nucleus

Mitochondrion Myofibril

N
F
S

N
I
M
D

I I

b c

(a) The diagram of cardiac muscle cells indicates their characteristic spaced intercalated discs (I) that cross the fibers. These irregular
features. The fibers consist of separate cells in a series joined at intercalated discs should not be confused with the repetitive,
interdigitating regions called the intercalated discs, which cross much more closely spaced striations (S), which are similar to those
an entire fiber between two cells. The transverse regions of the of skeletal muscle but less well-organized. Nuclei of fibroblasts in
steplike intercalated disc have abundant desmosomes and other endomysium are also present. (X200; H&E)
adherent junctions for firm adhesion, while longitudinal regions of (c) TEM showing an electron-dense intercalated disc with a step-
the discs are filled with gap junctions. like structure along the short interdigitating processes of adjacent
Cardiac muscle cells have central nuclei and myofibrils which are cardiac muscle cells. As shown here transverse disc regions have
usually sparser and less well-organized than those of skeletal muscle. many desmosomes (D) and adherent junctions called fascia
Also, the cells are often branched, allowing the muscle fibers to inter- adherentes (F) which join the cells firmly. Other regions of the disc
weave in a more complicated arrangement within fascicles which helps have abundant gap junctions which join the cells physiologically.
produce an e&cient contraction mechanism for emptying the heart. The sarcoplasm has numerous mitochondria (M) and myofibrillar
(b) Light microscopy of cardiac muscle in longitudinal section structures similar to those of skeletal muscle but slightly less orga-
show nuclei (N) in the center of the muscle fibers and widely nized. (X31,000)
 210 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–17 Cardiac muscle ultrastructure.

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D G

D
SR

a b

(a) TEM of cardiac muscle shows abundant mitochondria (M) and in the left atrium and the ventricles. The atrial granules contain
rather sparse sarcoplasmic reticulum (SR) in the areas between the precursor of a polypeptide hormone, atrial natriuretic fac-
myofibrils. T-tubules are less well-organized and are usually associ- tor (ANF). ANF targets cells of the kidneys to bring about sodium
ated with one expanded terminal cistern of SR, forming dyads (D) and water loss (natriuresis and diuresis). This hormone thus
rather than the triads of skeletal muscle. Functionally, these struc- opposes the actions of aldosterone and antidiuretic hormone,
tures are similar in these two muscle types. (X30,000) whose effects on kidneys result in sodium and water conserva-
(b) Muscle cells from the heart atrium show the presence of tion. (X10,000)
membrane-bound granules (G), mainly aggregated at the nuclear (Figure 10–17b, used with permission from Dr J.c. Nogueira,
poles. These granules are most abundant in muscle cells of the Department of Morphology, Federal University of Minas Gerais, Belo
right atrium (~600 per cell), but smaller quantities are also found Horizonte, Brazil.)

muscle is generated by myofibrillar arrays of actin and myosin thus serve as points for transmitting the contractile force
organized somewhat differently from those of striated muscle. not only within the cells, but also between adjacent cells
In smooth muscle cells bundles of thin and thick myofilaments (Figure 10–20). The endomysium and other connective tis-
crisscross the sarcoplasm obliquely. The myosin filaments sue layers help combine the force generated by the smooth
have a less regular arrangement among the thin filaments and muscle fibers into a concerted action, for example, peristal-
fewer crossbridges than in striated muscle. Moreover smooth sis in the intestine.
muscle actin filaments are not associated with troponin and Smooth muscle is not under voluntary motor control and
tropomyosin, using instead calmodulin and Ca2+-sensitive its fibers typically lack well-defined neuromuscular junctions.
myosin light-chain kinase (MLCK) to produce contraction. Contraction is most commonly stimulated by autonomic
The contraction mechanism, however, is basically similar to nerves, but in the gastrointestinal tract smooth muscle is also
that in striated muscle. controlled by various paracrine secretions and in the uterus by
As shown in Figure 10–20 the actin myofilaments oxytocin from the pituitary gland.
insert into anchoring cytoplasmic and plasmalemma- Axons of autonomic nerves passing through smooth
associated dense bodies which contain (-actinin and are muscle have periodic swellings or varicosities that lie in close
functionally similar to the Z discs of striated and cardiac contact with muscle fibers. Synaptic vesicles in the varicosities
muscle. Smooth muscle cells also have an elaborate array of release a neurotransmitter, usually acetylcholine or norepi-
10-nm intermediate filaments, composed of desmin, which nephrine, which diffuses and binds receptors in the sarcolem-
also attach to the dense bodies. The submembranous dense mae of numerous muscle cells. There is little or no specialized
bodies include cadherins of desmosomes linking adjacent structure to such junctions. As in cardiac muscle, stimulation
smooth muscle cells. Dense bodies in smooth muscle cells is propagated to more distant fibers via gap junctions that
 Smooth Muscle 211

FIGURE 10–18

C H A P T E R
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Smooth muscle.

XS

1 0
Muscle Tissue ■ Smooth Muscle
OL IC

P LS

a b

Cells or fibers of smooth muscle are long, tapering structures with elon-
gated nuclei centrally located at the cell’s widest part.
(a) In most of the digestive tract and certain similar structures smooth muscle is
organized into two layers which contract in a coordinated manner to produce a
A wave that moves the tract’s contents in a process termed peristalsis. In smooth
muscle of the small intestine wall cut in cross section, cells of the inner circular
(IC) layer are cut lengthwise and cells of the outer longitudinal layer (OL) are cut
transversely. Only some nuclei (arrows) of the latter cells are in the plane of sec-
tion so that many cells appear to be devoid of nuclei. (X140; H&E)
(b) Section of smooth muscle in bladder shows interwoven bundles of muscle
fibers in cross section (XS) and longitudinal section (LS) with the same fas-
cicle. There is much collagen in the branching perimysium (P), but the endo-
mysium can barely be seen by routine staining. (X140; Mallory trichrome)
(c) Section stained only for reticulin reveals the thin endomysium around
each fiber, with more reticulin in the connective tissue of small arteries (A).
Reticulin fibers associated with the basal laminae of smooth muscle cells
help hold the cells together as a functional unit during the slow, rhythmic
c contractions of this tissue. (X200; Silver)

allow all the smooth muscle cells to contract synchronously or Key histologic and functional features of smooth muscle,
in a coordinated manner. with comparisons to those of skeletal and cardiac muscle, are
In addition to contractile activity, smooth muscle cells summarized in Table 10–1.
also supplement fibroblast activity, synthesizing collagen,
elastin, and proteoglycans, with a major influence on the
ECM in tissues where these contractile cells are abundant.
› › MEDICAL APPLICATION
Benign tumors called leiomyomas commonly develop from
Active synthesis of ECM by the small cells/fibers of smooth
smooth muscle fibers but are seldom problematic. They most fre-
muscle may reflect less specialization for strong contractions
quently occur in the wall of the uterus, where they are more com-
than in skeletal and cardiac muscle and is similar to this syn-
monly called fibroids and where they can become su&ciently
thetic function in other contractile cells, such as myofibro-
large to produce painful pressure and unexpected bleeding.
blasts and pericytes.
 212 CHAPTER 10 ■ Muscle Tissue

FIGURE 10–19 Smooth muscle ultrastructure.

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N
DB

C
a b
N

(a) TEM of a transverse section of smooth muscle showing several (b) Longitudinal section showing several dense bodies (DB) in
cells sectioned at various points along their lengths, yielding profiles the cytoplasm and at the cell membrane. Both thin filaments and
of various diameters with only the largest containing a nucleus. Thick intermediate filaments attach to the dense bodies. Near the nucleus
and thin filaments are not organized into myofibril bundles and (N) are mitochondria, glycogen granules, and Golgi complexes. In
there are few mitochondria (M). A sparse external lamina surrounds both photos the cell membranes show invaginations called caveolae
each cell and reticular fibers are abundant in the ECM. A small unmy- (C) with various membrane proteins for cell signaling and regulating
elinated nerve (N) is also seen between the cells. (X6650) uptake and release of Ca2+ from sarcoplasmic reticulum. (X9000)

FIGURE 10–20 Smooth muscle contraction.

Thick filaments
Thin filaments

Dense body

Adjacent cells physically

coupled at dense bodies

CT

Nucleus

C
Dense body

a b

Most molecules that allow contraction are similar in the three types cytoskeleton and contractile apparatus allows the multicellular tissue
of muscle, but the filaments of smooth muscle are arranged differ- to contract as a unit, providing better e&ciency and force.
ently and appear less organized. (b) Micrograph showing a contracted (C) region of smooth muscle,
(a) The diagram shows that thin filaments attach to dense bodies with contraction decreasing the cell length and deforming the
located at the cell membrane and deep in the cytoplasm. Dense bod- nuclei. The long nuclei of individual fibers assume a cork-screw
ies contain α-actinin for thin filament attachment. Dense bodies at the shape when the fibers contract, reflecting the reduced cell length
membrane are also attachment sites for intermediate filaments and at contraction. Connective tissue (CT) of the perimysium outside
for adhesive junctions between cells. This arrangement of both the the muscle fascicle is stained blue. (X240; Mallory trichrome)
 Regeneration of Muscle Tissue 213

› REGENERATION OF MUSCLE TISSUE fuse with existing fibers to increase muscle mass beyond that
which occurs by cell hypertrophy. Following major traumatic

C H A P T E R
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The three types of adult muscle have different potentials injuries, scarring and excessive connective tissue growth inter-
for regeneration a%er injury which are also summarized in feres with skeletal muscle regeneration.
Table 10–1. Cardiac muscle lacks satellite cells and shows very little
In skeletal muscle, although the multinucleated cells regenerative capacity beyond early childhood. Defects or
cannot undergo mitosis, the tissue can still display limited damage (eg, infarcts) to heart muscle are generally replaced
regeneration. The source of regenerating cells is the sparse by proliferating fibroblasts and growth of connective tissue,

1 0
population of mesenchymal satellite cells lying inside the forming only myocardial scars.
external lamina of each muscle fiber. Satellite cells are inactive, Smooth muscle, composed of simpler, smaller, mononu-
reserve myoblasts which persist a%er muscle differentiation. cleated cells, is capable of a more active regenerative response.

Muscle Tissue ■ Regeneration of Muscle Tissue

A%er injury the normally quiescent satellite cells become acti- A%er injury, viable smooth muscle cells undergo mitosis and
vated, proliferating, and fusing to form new skeletal muscle replace the damaged tissue. As discussed in Chapter 11, con-
fibers. A similar activity of satellite cells has been implicated in tractile pericytes from the walls of small blood vessels partici-
muscle growth a%er extensive exercise, a process in which they pate in the repair of vascular smooth muscle.

Muscle Tissue SUMMARY OF KEY POINTS

■ There are three major types of muscle: (1) skeletal or striated mus- ■ When the membrane depolarization ends, Ca2+ is again seques-
cle, (2) cardiac muscle, and (3) smooth or visceral muscle. tered, ending contraction and allowing the sarcomeres to lengthen
■ Skeletal muscle cells are very long, multinucleated fibers, cylin- again as the muscle relaxes.
drically shaped and with diameters up to 100 μm. ■ Synapses of motor axons with skeletal muscle are called MEPs, NMJs,
■ The sarcolemma of each fiber is surrounded by an external lamina or myoneural junctions; the neurotransmitter is acetylcholine.
and thin connective tissue, endomysium, containing capillaries. ■ A motor axon may form many terminal branches, each ending on an
MEP of a muscle fiber; all fibers innervated by branches of that axon
Organization of Skeletal Muscle Fibers
comprise a motor unit.
■ Groups of fibers called fascicles are surrounded by perimysium; all
fascicles are enclosed within a dense connective tissue epimysium. Muscle Spindles & Tendon Organs
■ Internally each muscle fiber is filled with myofibrils, composed of ■ These are both sensory proprioceptors in which sensory axons
thousands of thick myosin filaments and thin actin filaments, wrap around intrafusal fibers in small specialized fascicles or
highly organized into contractile units called sarcomeres. around myotendinous collagen bundles, respectively.
■ Within sarcomeres thick and thin filaments interdigitate; globular
myosin heads project from the thick filaments toward the F-actin Muscle Fiber Types
filaments, which are associated with tropomyosin and troponin. ■ Skeletal muscles contain fibers that can be physiologically classi-
■ Sarcomeres are separated by Z discs that bisect the light-staining I fied as the three main types: (1) slow, oxidative (type I); (2) fast,
bands that contain mainly the thin filaments attached to α-actinin intermediate oxidative-glycolytic (type IIa); and (3) fast, glycolytic
in the Z disc. (type IIb).
■ Between the two I bands of a sarcomere is the dark-staining A
Cardiac Muscle
band with the thick myosin filaments; alternating light and dark
bands appear as microscopic striations along the fibers. ■ Cardiac muscle fibers are also striated, but they consist of individ-
ual cylindrical cells, each containing one (or two) central nuclei
Sarcoplasmic Reticulum & Transverse Tubule System and linked by adherent and gap junctions at prominent intercalated
■ In the sarcoplasm between parallel myofibrils are mitochondria discs.
and cisternae of smooth ER, called the sarcoplasmic reticulum ■ Sarcomeres of cardiac muscle are organized and function similarly
(SR) specialized for Ca2+ sequestration and release. to those of skeletal muscle.
■ At each sarcomere, two terminal cisterns of SR contact a deep ■ Contraction of cardiac muscle is intrinsic at nodes of impulse-gen-
invagination of the sarcolemma called a transverse or T-tubule, erating pacemaker muscle fibers; autonomic nerves regulate the
forming a triad that triggers Ca2+ release when the sarcolemma is rate of contraction.
depolarized.
Smooth Muscle
Mechanism of Contraction ■ Smooth muscle fibers are individual small, fusiform (tapering)
■ Ca2+ binding to troponin causes tropomyosin to change shape cells, linked by numerous gap junctions.
and allow the myosin heads to bind the actin subunits, forming ■ Thin and thick filaments in smooth muscle fibers do not form sar-
crossbridges between thick and thin filaments. comeres, and no striations are present.
■ The myosin heads then pivot with ATP hydrolysis, which pulls the ■ Thin actin filaments attach to (-actinin located in dense bodies that
thin filaments along the thick filaments. are located throughout the sarcoplasm and near the sarcolemma;
■ With Ca2+ and ATP present, a contraction cycle ensues in which contraction causes cells to shorten individually.
myosin heads repeatedly attach, pivot, detach, and return, ■ Sarcoplasmic reticulum is less well-organized in smooth muscle
causing the filaments to slide past one another, shortening the fibers, and there is no transverse tubule system.
sarcomere.
 214 CHAPTER 10 ■ Muscle Tissue

■ Troponin is lacking in smooth muscle; proteins controlling the ■ Cardiac muscle lacks satellite cells and has little capacity for
sliding filaments here include myosin light-chain kinase (MLCK) regeneration.
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and the Ca2+-binding protein calmodulin. ■ Regeneration is rapid in smooth muscle because the cells/fibers are
small and relatively less differentiated, which allow renewed mitotic
Regeneration of Muscle Tissue activity a%er injury.
■ Repair and regeneration can occur in skeletal muscle because of
a population of reserve muscle satellite cells that can proliferate,
fuse, and form new muscle fibers.

Muscle Tissue ASSESS YOUR KNOWLEDGE

1. The basal lamina of a muscle fiber is part of which structure? 7. In one type of muscle, numerous gap junctions, desmosomes, and
a. Perimysium adherens junctions are specifically localized in which structures?
b. Epimysium a. Myofilaments
c. Fascia b. Dense bodies
d. Endomysium c. Sarcomeres
e. Sarcoplasmic reticulum d. Neuromuscular spindles
e. Intercalated discs
2. With the transmission electron microscope skeletal muscle fibers
can be seen to contain structures called triads. What do the two 8. A 66-year-old man who lives alone has a severe myocardial infarc-
lateral components of a triad represent? tion and dies during the night. The medical examiner’s o)ce is called
a. Attachment sites for thick myofilaments the following morning and describes the man’s body as being in rigor
b. Sites for calcium sequestration and release mortis. This state of rigor mortis is due to which one of the following?
c. Sites for impulse conduction into the fiber a. Inhibition of Ca2+ leakage from the extracellular fluid and sarco-
d. Sites for ATP production plasmic reticulum
e. Sites for synthesis of proteins to be secreted outside the cell b. Enhanced retrieval of Ca2+ by the sarcoplasmic reticulum
c. Failure to disengage tropomyosin and troponin from the myosin
3. Which characteristic is unique to cardiac muscle?
active sites
a. Contain centrally located nuclei d. Absence of ATP preventing detachment of the myosin heads
b. Striated from actin
c. O%en branched e. Increased lactic acid production
d. Multinucleated
e. Lack T-tubules 9. A 5-year-old boy sustains a small tear in his gastrocnemius muscle
when he is involved in a bicycle accident. Regeneration of the muscle
4. In smooth muscle calcium released by the smooth ER initiates con- will occur through which of the following mechanisms?
traction by binding to what protein?
a. Dedifferentiation of muscle cells into myoblasts
a. Actin b. Differentiation of muscle satellite cells
b. Calmodulin c. Fusion of damaged myofibers to form new myotubes
c. Desmin d. Hyperplasia of existing muscle fibers
d. Myosin light chain kinase e. Differentiation of fibroblasts to form myoblasts
e. Tropomyosin
10. A healthy 32-year-old man li%s weights regularly as part of his work-
5. Which feature typifies T-tubules? out. In one of his biceps muscle fibers at rest, the length of the I band
a. Evaginations of the sarcoplasmic reticulum is 1.0 μm and the A band is 1.5 μm. Contraction of that muscle fiber
b. Sequester calcium during muscle relaxation, releasing it during results in a 10% shortening of the length of the sarcomere. What is
contraction the length of the A band a%er the shortening produced by muscle
c. Carry depolarization to the muscle fiber interior contraction?
d. Overlie the A-I junction in cardiac muscle cells a. 1.50 μm
e. Rich supply of acetylcholine receptors b. 1.35 μm
6. Which characteristic is unique to smooth muscle? c. 1.00 μm
d. 1.90 μm
a. T-tubules lie across Z lines
e. 0.45 μm
b. Each thick filament is surrounded by six thin filaments
c. Thin filaments attach to dense bodies
d. Cells are multinucleated
e. Cells have centrally located nuclei

Answers: 1d, 2b, 3c, 4b, 5c, 6c, 7e, 8d, 9b, 10a