and Muscle Tissue - PHSchool.com

9

Overview of Muscle Tissues Muscles
(pp. 276–277) and Muscle

Types of Muscle Tissue (p. 276) Tissue

Special Characteristics of Muscle Because flexing muscles look like mice scurrying beneath the skin,
Tissue (p. 276) some scientist long ago dubbed them muscles, from the Latin mus
meaning “little mouse.” Indeed, we tend to think of the rippling
Muscle Functions (pp. 276–277) muscles of professional boxers or weight lifters when we hear the word
muscle. But muscle is also the dominant tissue in the heart and in the
Skeletal Muscle (pp. 277–305) walls of other hollow organs. In all its forms, muscle tissue makes up
nearly half the body’s mass. Muscles are distinguished by their ability to
Gross Anatomy of a Skeletal Muscle transform chemical energy (ATP) into directed mechanical energy. In
(pp. 277–278) so doing, they become capable of exerting force.

Microscopic Anatomy of a Skeletal Muscle 275
Fiber (pp. 278–284)

Sliding Filament Model of Contraction (p. 284)

Physiology of Skeletal Muscle Fibers
(pp. 284–289)

Contraction of a Skeletal Muscle (pp. 289–296)

Muscle Metabolism (pp. 296–300)

Force of Muscle Contraction (pp. 300–302)

Velocity and Duration of Contraction
(pp. 302–303)

Effect of Exercise on Muscles (pp. 304–305)

Smooth Muscle (pp. 305–311)

Microscopic Structure of Smooth Muscle Fibers
(pp. 305–307)

Contraction of Smooth Muscle (pp. 307–311)

Types of Smooth Muscle (p. 311)

Developmental Aspects of Muscles
(pp. 311–312, 316)

276 UNIT 2 Covering, Support, and Movement of the Body

Overview of Muscle Tissues Special Characteristics of Muscle Tissue

᭤ Compare and contrast the basic types of muscle tissue. What enables muscle tissue to perform its duties? Four special
characteristics or abilities are key.
᭤ List four important functions of muscle tissue.
Excitability, also termed responsiveness or irritability, is
Types of Muscle Tissue the ability to receive and respond to a stimulus, that is, any
change in the environment either inside or outside the body. In
The three types of muscle tissue—skeletal, cardiac, and the case of muscle, the stimulus is usually a chemical—for ex-
smooth—were introduced in Chapter 4. Now we are ready to ample, a neurotransmitter released by a nerve cell, or a local
describe the three types of muscle tissue in detail, but before we change in pH. The response (sometimes separated out as an ad-
do, let’s introduce some terminology. First, skeletal and smooth ditional characteristic called conductivity), is generation of an
muscle cells (but not cardiac muscle cells) are elongated, and electrical impulse that passes along the plasma membrane of
for this reason, are called muscle fibers. Second, whenever you the muscle cell and causes the cell to contract.
see the prefixes myo or mys (both are word roots meaning
“muscle”) or sarco (flesh), the reference is to muscle. For ex- Contractility is the ability to shorten forcibly when ade-
ample, the plasma membrane of muscle cells is called the quately stimulated. This ability sets muscle apart from all other
sarcolemma (sarЉko-lemЈah), literally, “muscle” (sarco) “husk” tissue types.
(lemma), and muscle cell cytoplasm is called sarcoplasm. Okay,
9 let’s get to it. Extensibility is the ability to be stretched or extended. Muscle
cells shorten when contracting, but they can be stretched, even
Skeletal muscle tissue is packaged into the skeletal muscles, beyond their resting length, when relaxed.
organs that attach to and cover the bony skeleton. Skeletal mus-
cle fibers are the longest muscle cells and have obvious stripes Elasticity is the ability of a muscle cell to recoil and resume
called striations (see Figure 4.10a, p. 136). Although it is often its resting length after being stretched.
activated by reflexes, skeletal muscle is called voluntary muscle
because it is the only type subject to conscious control. When Muscle Functions
you think of skeletal muscle tissue, the key words to keep in
mind are skeletal, striated, and voluntary. Muscle performs at least four important functions for the body.
It produces movement, maintains posture, stabilizes joints, gen-
Skeletal muscle is responsible for overall body mobility. It erates heat, and more.
can contract rapidly, but it tires easily and must rest after short
periods of activity. Nevertheless, it can exert tremendous power, Producing Movement
a fact revealed by reports of people lifting cars to save their loved
ones. Skeletal muscle is also remarkably adaptable. For example, Just about all movements of the human body and its parts result
your hand muscles can exert a force of a fraction of an ounce to from muscle contraction. Skeletal muscles are responsible for all
pick up a paper clip, and the same muscles can exert a force of locomotion and manipulation. They enable you to respond
about 70 pounds to pick up this book! quickly to changes in the external environment—for example,
to jump out of the way of a car, to direct your eyeballs, and to
Cardiac muscle tissue occurs only in the heart (the body’s smile or frown.
blood pump), where it constitutes the bulk of the heart walls.
Like skeletal muscle cells, cardiac muscle cells are striated (see Blood courses through your body because of the rhythmically
Figure 4.10b, p. 137), but cardiac muscle is not voluntary. In- beating cardiac muscle of your heart and the smooth muscle in
deed, it can and does contract without being stimulated by the the walls of your blood vessels, which helps maintain blood pres-
nervous system. Most of us have no conscious control over how sure. Smooth muscle in organs of the digestive, urinary, and re-
fast our heart beats. Key words to remember for cardiac muscle productive tracts propels, or squeezes, substances (foodstuffs,
are cardiac, striated, and involuntary. urine, a baby) through the organs and along the tract.

Cardiac muscle usually contracts at a fairly steady rate set by Maintaining Posture and Body Position
the heart’s pacemaker, but neural controls allow the heart to
speed up for brief periods, as when you race across the tennis We are rarely aware of the workings of the skeletal muscles that
court to make that overhead smash. maintain body posture. Yet these muscles function almost con-
tinuously, making one tiny adjustment after another to counter-
Smooth muscle tissue is found in the walls of hollow vis- act the never-ending downward pull of gravity.
ceral organs, such as the stomach, urinary bladder, and respira-
tory passages. Its role is to force fluids and other substances Stabilizing Joints
through internal body channels. Smooth muscle cells like skele-
tal muscle cells are elongated “fibers,” but smooth muscle has no Even as muscles pull on bones to cause movements, they stabi-
striations (see Figure 4.10c, p. 137). Like cardiac muscle, it is not lize and strengthen the joints of the skeleton (Chapter 8).
subject to voluntary control. Contractions of smooth muscle
fibers are slow and sustained. We can describe smooth muscle Generating Heat
tissue as visceral, nonstriated, and involuntary.
Muscles generate heat as they contract. This heat is vitally im-
portant in maintaining normal body temperature. Because

Chapter 9 Muscles and Muscle Tissue 277

skeletal muscle accounts for at least 40% of body mass, it is the and smooth muscle tissues, which can contract in the absence of
muscle type most responsible for generating heat. nerve stimulation, each skeletal muscle fiber is supplied with a
nerve ending that controls its activity.
Additional Functions
What else do muscles do? Skeletal muscles protect the more Skeletal muscle has a rich blood supply. This is understand-
fragile internal organs (the viscera) by enclosing them. Smooth able because contracting muscle fibers use huge amounts of en-
muscle also forms valves to regulate the passage of substances ergy and require more or less continuous delivery of oxygen and
through internal body openings, dilates and constricts the nutrients via the arteries. Muscle cells also give off large
pupils of your eyes, and forms the arrector pili muscles attached amounts of metabolic wastes that must be removed through
to hair follicles. veins if contraction is to remain efficient. Muscle capillaries, the
smallest of the body’s blood vessels, are long and winding and
■■■ have numerous cross-links, features that accommodate changes
in muscle length. They straighten when the muscle is stretched
In much of this chapter, we examine the structure and func- and contort when the muscle contracts.
tion of skeletal muscle. Then we consider smooth muscle more
briefly, largely by comparing it with skeletal muscle. We describe Connective Tissue Sheaths 9
cardiac muscle in detail in Chapter 18, but for easy comparison,
the characteristics of all three muscle types are included in the In an intact muscle, the individual muscle fibers are wrapped
summary in Table 9.3 on p. 309. and held together by several different connective tissue sheaths.
Together these connective tissue sheaths support each cell and
CHECK YOUR UNDERSTANDING reinforce the muscle as a whole, preventing the bulging muscles
from bursting during exceptionally strong contractions. We will
1. When describing muscle, what does “striated” mean? consider these from external to internal (see Figure 9.1 and the
2. Harry was pondering an exam question that said, “What top three rows of Table 9.1).

muscle type has elongated cells and is found in the walls of 1. Epimysium. The epimysium (epЉ˘ı-misЈe-um; meaning
the urinary bladder?” What should he have responded? “outside the muscle”) is an “overcoat” of dense irregular
connective tissue that surrounds the whole muscle. Some-
For answers, see Appendix G. times it blends with the deep fascia that lies between neigh-
boring muscles or the superficial fascia deep to the skin.
Skeletal Muscle
2. Perimysium and fascicles. Within each skeletal muscle, the
᭤ Describe the gross structure of a skeletal muscle. muscle fibers are grouped into fascicles (fasЈ˘ı-klz; “bun-
᭤ Describe the microscopic structure and functional roles of dles”) that resemble bundles of sticks. Surrounding each
fascicle is a layer of fibrous connective tissue called
the myofibrils, sarcoplasmic reticulum, and T tubules of perimysium (perЉ˘ı-misЈe-um; meaning “around the mus-
skeletal muscle fibers. cle [fascicles]”).

᭤ Describe the sliding filament model of muscle contraction. 3. Endomysium. The endomysium (enЉdo-misЈe-um; mean-
ing “within the muscle”) is a whispy sheath of connective
For easy reference, Table 9.1 summarizes the levels of skeletal tissue that surrounds each individual muscle fiber. It con-
muscle organization, gross to microscopic, that we describe in sists of fine areolar connective tissue.
the following sections.
As shown in Figure 9.1, all of these connective tissue sheaths
Gross Anatomy of a Skeletal Muscle are continuous with one another as well as with the tendons that
join muscles to bones. When muscle fibers contract, they pull on
Each skeletal muscle is a discrete organ, made up of several these sheaths, which in turn transmit the pulling force to the
kinds of tissues. Skeletal muscle fibers predominate, but blood bone to be moved. The sheaths contribute somewhat to the nat-
vessels, nerve fibers, and substantial amounts of connective tis- ural elasticity of muscle tissue, and also provide entry and exit
sue are also present. A skeletal muscle’s shape and its attach- routes for the blood vessels and nerve fibers that serve the muscle.
ments in the body can be examined easily without the help of a
microscope. Attachments

Nerve and Blood Supply Recall from Chapter 8 that most skeletal muscles span joints
In general, each muscle is served by one nerve, an artery, and by and are attached to bones (or other structures) in at least two
one or more veins. These structures all enter or exit near the places, and that when a muscle contracts, the movable bone, the
central part of the muscle and branch profusely through its con- muscle’s insertion, moves toward the immovable or less mov-
nective tissue sheaths (described below). Unlike cells of cardiac able bone, the muscle’s origin. In the muscles of the limbs, the
origin typically lies proximal to the insertion.

Muscle attachments, whether origin or insertion, may be di-
rect or indirect. In direct, or fleshy, attachments, the epimy-
sium of the muscle is fused to the periosteum of a bone or







Chapter 9 Muscles and Muscle Tissue 281

fiber, depending on its size, and they account for about 80% of lap. Notice that each thick filament is actually surrounded by a
cellular volume. These myofibrils contain the contractile ele- hexagonal arrangement of six thin filaments, and each thin fila-
ments of skeletal muscle cells, the sarcomeres, which contain ment is enclosed by three thick filaments.
even smaller rodlike structures called myofilaments. Table 9.1
(bottom three rows) summarizes these structures, which we dis- Ultrastructure and Molecular Composition of the Myofilaments 9
cuss next.
Muscle contraction depends on the myosin- and actin-containing
Striations, Sarcomeres, and Myofilaments Striations, a re- myofilaments. As noted earlier, thick filaments (about 16 nm in
peating series of dark and light bands, are evident along the diameter) are composed primarily of the protein myosin. Each
length of each myofibril. In an intact muscle fiber, the dark myosin molecule consists of two heavy and four light polypep-
A bands and light I bands are nearly perfectly aligned with one tide chains, and has a rodlike tail attached by a flexible hinge to
another, giving the cell as a whole its striated appearance. two globular heads (Figure 9.3). The tail consists of two inter-
twined helical polypeptide heavy chains. The globular heads,
As illustrated in Figure 9.2c, each dark A band has a lighter each associated with two light chains, are the “business end” of
region in its midsection called the H zone (H for helle; “bright”). myosin. During contraction, they link the thick and thin fila-
Each H zone is bisected vertically by a dark line called the M line ments together, forming cross bridges (Figure 9.4), and swivel
(M for middle) formed by molecules of the protein myomesin. around their point of attachment. As we will explain shortly,
The light I bands also have a midline interruption, a darker area these cross bridges act as motors to generate the tension devel-
called the Z disc (or Z line). oped by a contracting muscle cell.

A sarcomere (sarЈko-me˘r; literally, “muscle segment”) is the Each thick filament contains about 300 myosin molecules
smallest contractile unit of a muscle fiber—the functional unit bundled together with their tails forming the central part of the
of skeletal muscle. Averaging 2 µm long, a sarcomere is the re- thick filament and their heads facing outward and at each end
gion of a myofibril between two successive Z discs. In other (Figure 9.3). As a result, the central portion of a thick filament
words, it contains an A band flanked by half an I band at each (in the H zone) is smooth, but its ends are studded with a stag-
end (Figure 9.2c). Within each myofibril, the sarcomeres are gered array of myosin heads. The heads bear actin and ATP-
aligned end-to-end like boxcars in a train. binding sites and also contain ATPase enzymes that split ATP to
generate energy for muscle contraction.
If we examine the banding pattern of a myofibril at the mo-
lecular level, we see that it arises from an orderly arrangement of The thin filaments (7–8 nm thick) are composed chiefly of
two types of even smaller structures within the sarcomeres. the protein actin (blue in Figure 9.3). Actin has kidney-shaped
These smaller structures, the myofilaments or filaments, are polypeptide subunits, called globular actin or G actin, which
the muscle equivalents of the actin- or myosin-containing mi- bear the active sites to which the myosin heads attach during
crofilaments described in Chapter 3. As you will recall, the pro- contraction. In the thin filaments, G actin subunits are poly-
teins actin and myosin play a role in motility and shape changes merized into long actin filaments called fibrous, or F, actin. The
in virtually every cell in the body. This property reaches its high- backbone of each thin filament appears to be formed by two in-
est development in the contractile muscle fibers. tertwined actin filaments that look like a twisted double strand
of pearls (Figure 9.3).
As you can see in Figure 9.2c and d, the central thick filaments
containing myosin (red) extend the entire length of the A Several regulatory proteins are also present in thin filaments.
band. The more lateral thin filaments containing actin (blue) Polypeptide strands of tropomyosin (troЉpo-miЈo-sin), a rod-
extend across the I band and partway into the A band. The shaped protein, spiral about the actin core and help stiffen and
Z disc, a coin-shaped sheet composed largely of the protein stabilize it. Successive tropomyosin molecules are arranged end-
alpha-actinin, anchors the thin filaments. The third type of to-end along the actin filaments, and in a relaxed muscle fiber,
myofilament illustrated in Figure 9.2d, the elastic filament, is they block myosin-binding sites on actin so that the myosin
described in the next section. Intermediate (desmin) fila- heads on the thick filaments cannot bind to the thin filaments.
ments (not illustrated) extending from the Z disc connect The other major protein in thin filaments is troponin (troЈpo-
each myofibril to the next throughout the width of the mus- nin), a globular three-polypeptide complex (Figure 9.3). One of
cle cell. its polypeptides (TnI) is an inhibitory subunit that binds to
actin. Another (TnT) binds to tropomyosin and helps position
Looking at the banding pattern more closely, we see that the it on actin. The third (TnC) binds calcium ions. Both troponin
H zone of the A band appears less dense because the thin fila- and tropomyosin help control the myosin-actin interactions
ments do not extend into this region. The M line in the center of involved in contraction.
the H zone is slightly darker because of the presence there of
fine protein strands that hold adjacent thick filaments together. The elastic filament we referred to earlier is composed of the
The myofilaments are connected to the sarcolemma and held in giant protein titin (Figure 9.2d). This protein extends from the
register at the Z discs and the M lines. Z disc to the thick filament, and then runs within the thick fila-
ment (forming its core) to attach to the M line. It holds the thick
A longitudinal view of the myofilaments such as that in filaments in place, thus maintaining the organization of the A
Figure 9.2d is a bit misleading because it looks as if each thick band, and helps the muscle cell to spring back into shape after
(red) filament interdigitates with only four thin (blue) fila- being stretched. (The part of the titin that spans the I bands is
ments. The cross section of a sarcomere on the far right in extensible, unfolding when the muscle is stretched and recoiling
Figure 9.2e shows an area where thick and thin filaments over-

282 UNIT 2 Covering, Support, and Movement of the Body
Longitudinal section of filaments within one
sarcomere of a myofibril

Thick filament

Thin filament

In the center of the sarcomere, the thick filaments
lack myosin heads. Myosin heads are present only
in areas of myosin-actin overlap.

9 Thin filament
Thick filament

Each thick filament consists of many myosin molecules A thin filament consists of two strands of actin subunits
whose heads protrude at opposite ends of the filament. twisted into a helix plus two types of regulatory proteins

Portion of a thick filament (troponin and tropomyosin).
Portion of a thin filament

Myosin head Tropomyosin Troponin Actin

Actin-binding sites

Heads Tail
Flexible hinge region
ATP- Actin subunits Active sites
binding for myosin
site attachment

Myosin molecule Actin subunits

Figure 9.3 Composition of thick and thin filaments.

when the tension is released.) Titin does not resist stretching in Sarcoplasmic Reticulum and T Tubules
the ordinary range of extension, but it stiffens as it uncoils, help-
ing the muscle to resist excessive stretching, which might pull Skeletal muscle fibers contain two sets of intracellular tubules
the sarcomeres apart. that participate in regulation of muscle contraction: (1) the sar-
coplasmic reticulum and (2) T tubules.
Another important structural protein is dystrophin, which
links the thin filaments to the integral proteins of the sar- Sarcoplasmic Reticulum Shown in blue in Figure 9.5, the
colemma (which in turn are anchored to the extracellular sarcoplasmic reticulum (SR) is an elaborate smooth endoplas-
matrix). Other proteins that act to bind filaments or sarcomeres mic reticulum (see p. 84–85). Its interconnecting tubules
together and maintain their alignment include nebulin, myo- surround each myofibril the way the sleeve of a loosely cro-
mesin, and C proteins. cheted sweater surrounds your arm. Most of these tubules run

Chapter 9 Muscles and Muscle Tissue 283

Thin filament (actin) Myosin heads Thick filament (myosin) The major role of the SR is to regulate intracellular levels of
ionic calcium. It stores calcium and releases it on demand when
the muscle fiber is stimulated to contract. As you will see, cal-
cium provides the final “go” signal for contraction.

Figure 9.4 Transmission electron micrograph of part of a sar- T Tubules At each A band–I band junction, the sarcolemma of 9
comere clearly showing the myosin heads forming cross the muscle cell protrudes deep into the cell interior, forming
bridges that generate the contractile force. (277,000ϫ) an elongated tube called the T tubule (T for “transverse”). The
T tubules, shown in gray in Figure 9.5, tremendously increase
longitudinally along the myofibril communicating at the H zone. the muscle fiber’s surface area. Possibly the result of fusing tube-
Others called terminal cisternae (“end sacs”) form larger, per- like caveolae (inpocketings of the sarcolemma), the lumen of
pendicular cross channels at the A band–I band junctions and the T tubule is continuous with the extracellular space. Along its
they always occur in pairs. Closely associated with the SR are length, each T tubule runs between the paired terminal cister-
large numbers of mitochondria and glycogen granules, both nae of the SR, forming triads, successive groupings of the three
involved in producing the energy used during contraction. membranous structures (terminal cisterna, T tubule, and termi-
nal cisterna). As they pass from one myofibril to the next, the
T tubules also encircle each sarcomere.

Muscle contraction is ultimately controlled by nerve-initiated
electrical impulses that travel along the sarcolemma. Because
T tubules are continuations of the sarcolemma, they conduct
impulses to the deepest regions of the muscle cell and to every
sarcomere. These impulses signal for the release of calcium from
the adjacent terminal cisternae. You can think of the T tubules as

Part of a skeletal I band A band I band
muscle fiber (cell) Z disc Z disc
H zone
M
line

Myofibril Sarcolemma

Sarcolemma Triad:
• T tubule
• Terminal

cisternae
of the SR (2)

Tubules of
the SR

Myofibrils

Mitochondria

Figure 9.5 Relationship of the sarcoplasmic reticulum and T tubules to myofibrils of
skeletal muscle. The tubules of the SR (blue) encircle each myofibril like a “holey” sleeve.
These tubules fuse to form a net of communicating channels at the level of the H zone and
saclike elements called terminal cisternae abutting the A-I junctions. The T tubules (gray) are
inward invaginations of the sarcolemma that run deep into the cell between the terminal
cisternae. Sites of close contact of these three elements (terminal cisterna, T tubule, and
terminal cisterna) are called triads.

284 UNIT 2 Covering, Support, and Movement of the Body

ZH Sliding Filament Model of Contraction
IA
1 Fully relaxed sarcomere of a muscle fiber We almost always think “shortening” when we hear the word
contraction, but to physiologists the term refers only to the acti-
9 vation of myosin’s cross bridges, which are the force-generating
sites. Shortening occurs if and when the tension generated by the
cross bridges on the thin filaments exceeds the forces opposing
shortening and pulls the thin filaments toward the M line. Con-
traction ends when the cross bridges become inactive and the
tension declines, inducing relaxation of the muscle fiber.

The sliding filament model of contraction states that dur-
ing contraction the thin filaments slide past the thick ones so
that the actin and myosin filaments overlap to a greater degree.
In a relaxed muscle fiber, the thick and thin filaments overlap
only at the ends of the A band (Figure 9.6, 1 ).
Z When muscle fibers are stimulated by the nervous system,
the myosin heads on the thick filaments latch onto myosin-
I binding sites on actin in the thin filaments, and the sliding be-
gins. These cross bridge attachments are formed and broken
several times during a contraction, acting like tiny ratchets to
generate tension and propel the thin filaments toward the center
of the sarcomere. As this event occurs simultaneously in sar-
comeres throughout the cell, the muscle cell shortens. Notice
that as the thin filaments slide centrally, the Z discs to which they
are attached are pulled toward the M line (Figure 9.6, 2 ).
Overall, as a muscle cell shortens, the I bands shorten, the dis-
tance between successive Z discs is reduced, the H zones disap-
pear, and the contiguous A bands move closer together but do
not change in length.

Z Z CHECK YOUR UNDERSTANDING
I
IA 3. How does the term epimysium relate to the role and position
2 Fully contracted sarcomere of a muscle fiber of this connective tissue sheath?

Figure 9.6 Sliding filament model of contraction. The num- 4. Which myofilaments have binding sites for calcium? What
bers indicate events in a 1 relaxed and a 2 fully contracted sar- specific molecule binds calcium?
comere. At full contraction, the Z discs abut the thick filaments and
the thin filaments overlap each other. The photomicrographs (top 5. Which structure—T tubule, mitochondrion, or SR—contains
view in each case) show enlargements of 29,200ϫ. the highest concentration of calcium ions in a resting muscle
fiber? Which structure provides the ATP needed for muscle
a rapid telegraph system that ensures that every myofibril in the activity?
muscle fiber contracts at virtually the same time.
For answers, see Appendix G.
Triad Relationships The roles of the T tubules and SR in pro-
viding signals for contraction are tightly linked. At the triads, Physiology of Skeletal Muscle Fibers
where these organelles come into closest contact, something
that resembles a double zipper of integral proteins protrudes ᭤ Explain how muscle fibers are stimulated to contract by
into the intermembrane spaces. The protruding integral pro- describing events that occur at the neuromuscular junction.
teins of the T tubule act as voltage sensors. Those of the SR,
called foot proteins, form gated channels through which Ca2ϩ ᭤ Describe how an action potential is generated.
can be released from the SR cisternae. We will return to consider ᭤ Follow the events of excitation-contraction coupling that
their interaction shortly.
lead to cross bridge activity.

The sliding filament model tells us how a muscle fiber contracts,
but what induces it to contract in the first place? For a skeletal
muscle fiber to contract

1. It must be activated, that is, stimulated by a nerve ending
so that a change in membrane potential occurs.





Chapter 9 Muscles and Muscle Tissue 287

Axon terminal

Open Na+ Closed K+
Channel Channel

Synaptic Na+ ______ _ _ _ _ _ _ _ _ _++ ++
cleft ____ _ _ _ _ _ _ _

ACh ++++++++++ ++++ +++++++_ _ _ _ 9
++++++ K+ ++++++
ACh Na+ K+ of depolarization +
Na+ K+ Action potential

Wave 2 Generation and propagation of the action potential (AP)
Membrane areas adjacent to the neuromuscular junction are
1 Local depolarization: generation of the end depolarized by spread of the local current. This opens
plate potential on the sarcolemma voltage-gated sodium channels there, so Na+ enters, following
Binding of ACh to ACh receptors opens the its electrochemical gradient, and initiates the AP.
chemically gated ion channels housed in the ACh
receptors allowing both Na+ and K+ to pass. The action potential is propagated as the local
depolarization wave spreads to adjacent areas of the
Because more Na+ diffuses in than K+ diffuses sarcolemma and opens voltage-gated sodium channels there.
out, a transient change in membrane potential, Again, sodium ions, normally restricted from entering, diffuse
called depolarization, occurs so that the interior of into the cell following their electrochemical gradient.
the sarcolemma at that point becomes slightly less
negative. This local electrical event is called the end Closed Na+ Open K+
plate potential. Channel Channel

Sarcoplasm of muscle fiber Na+ +++++++++++

+++++++++ +++

________ ____ ___________

K+

3 Repolarization
This stage restores the sarcolemma to its initial polarized state.

Repolarization quickly follows the depolarization wave and
occurs as Na+ channels close (inactivate) and voltage-gated K+
channels open. Because K+ concentration is substantially higher
inside the cell than in the extracellular fluid, K+ diffuses rapidly

out of the muscle fiber down its concentration gradient.

Figure 9.9 Summary of events in the generation and propagation of an action potential
in a skeletal muscle fiber. The axon terminal plasma membrane and the sarcolemma are
shown at different scales.

neuromuscular junction opens chemically (ligand) gated 2 Generation and propagation of the action potential.
ion channels that allow Naϩ and Kϩ to pass (also see Figure
9.8). Because more Naϩ diffuses in than Kϩ diffuses out, a Initially, depolarization is a local electrical event called an
transient change in membrane potential occurs as the inte- end plate potential, but it ignites the action potential that
rior of the sarcolemma becomes slightly less negative, an spreads in all directions from the neuromuscular junction
event called depolarization. across the sarcolemma, just as ripples move away from peb-
bles dropped into a stream. This local depolarization (end
plate potential) then spreads to adjacent membrane areas

288 UNIT 2 Covering, Support, and Movement of the Body

Membrane potential (mV)+30 Na+ channels sarcolemma leads to the sliding of myofilaments. The action
close, K+ channels potential is brief and ends well before any signs of contraction
Depolarization open are obvious. The events of excitation-contraction coupling occur
due to Na+ entry during the latent period (laten = hidden), between action poten-
0 Repolarization tial initiation and the beginning of mechanical activity (contrac-
due to K+ exit tion). As you will see, the electrical signal does not act directly on
Na+ the myofilaments. Instead, it causes the rise in intracellular
channels 12 Threshold calcium ion concentration that allows the filaments to slide.
open Time (ms)
K+ channels Focus on Excitation-Contraction Coupling (Figure 9.11) on
–55 close pp. 290–291 illustrates the steps in this process. This Focus fea-
–70 ture also reveals how the integral proteins of the “double zip-
34 pers” in the triads interact to provide the Ca2ϩ necessary for
0 contraction to occur. Make sure you understand this material
before continuing on.
Figure 9.10 Action potential scan showing changes in Na؉ and
9 K؉ ion channels. Summary of Different Types of Channels
Involved in Initiating Muscle Contraction
and opens voltage-gated (p. 81) sodium channels there.
Naϩ enters, following its electrochemical gradient, and So let’s summarize what has to happen from the nerve ending
once a certain membrane voltage, referred to as threshold, is on to finally excite muscle cells. Essentially this process involves
reached, an action potential is generated (initiated). activation of four sets of ion channels:

The action potential is propagated (moves along the 1. The process is initiated when the nerve impulse reaches
length of the sarcolemma) as the local depolarization wave the neuron terminal and opens voltage-gated calcium
spreads to adjacent areas of the sarcolemma and opens channels in the axonal membrane. Calcium entry triggers
voltage-gated sodium channels there. Again, Naϩ, normally release of ACh into the synaptic cleft.
restricted from entering, diffuses into the cell following its
electrochemical gradient. 2. Released ACh binds to ACh receptors in the sarcolemma,
opening chemically gated Naϩ-Kϩ channels. Greater in-
3 Repolarization. The sarcolemma is restored to its initial po- flux of Naϩ causes a local voltage change (the end plate
larized state during repolarization. The repolarization potential).
wave, like the depolarization wave, is a consequence of
changes in membrane permeability. In this case, Naϩ chan- 3. Local depolarization opens voltage-gated sodium chan-
nels close and voltage-gated Kϩ channels open. Since the nels in the neighboring region of the sarcolemma. This al-
potassium ion concentration is substantially higher inside lows more sodium to enter, which further depolarizes the
the cell than in the extracellular fluid, Kϩ diffuses rapidly sarcolemma, resulting in AP generation and propagation.
out of the muscle fiber, restoring negatively charged condi-
tions inside (also see Figure 9.10). 4. Transmission of an AP along the T tubules changes the
shape of voltage-sensitive proteins in the T tubules, which
During repolarization, a muscle fiber is said to be in a in turn stimulate SR calcium release channels to release
refractory period, because the cell cannot be stimulated again Ca2ϩ into the cytosol.
until repolarization is complete. Note that repolarization re-
stores only the electrical conditions of the resting (polarized) Muscle Fiber Contraction: Cross Bridge Activity
state. The ATP-dependent Naϩ-Kϩ pump restores the ionic con-
ditions of the resting state, but hundreds of action potentials can As we have noted, cross bridge formation (attachment of
occur before ionic imbalances interfere with contractile activity. myosin heads to actin) requires Ca2ϩ. Let’s look more closely at
how calcium ions promote muscle cell contraction. When intra-
Once initiated, the action potential is unstoppable. It ulti- cellular calcium levels are low, the muscle cell is relaxed, and the
mately results in contraction of the muscle fiber. Although the active (myosin-binding) sites on actin are physically blocked by
action potential itself is very brief, only 1–2 milliseconds (ms), tropomyosin molecules. As Ca2ϩ levels rise, the ions bind to
the contraction phase of a muscle fiber may persist for 100 ms regulatory sites on troponin. To activate its group of seven
or more and far outlasts the electrical event that triggers it. actins, a troponin must bind two calcium ions, change shape,
and then roll tropomyosin into the groove of the actin helix,
Excitation-Contraction Coupling away from the myosin-binding sites. In short, the tropomyosin
“blockade” is removed when sufficient calcium is present. Once
Excitation-contraction (E-C) coupling is the sequence of binding sites on actin are exposed, the events of the cross bridge
events by which transmission of an action potential along the cycle occur in rapid succession, as depicted in Focus on the Cross
Bridge Cycle (Figure 9.12) on p. 292.

Sliding of thin filaments continues as long as the calcium sig-
nal and adequate ATP are present. When nerve impulses are de-
livered rapidly, intracellular Ca2ϩ levels increase greatly due to
successive “puffs” or rounds of Ca2ϩ released from the SR. In

Chapter 9 Muscles and Muscle Tissue 289

such cases, the muscle cells do not completely relax between Contraction of a Skeletal Muscle
successive stimuli and contraction is stronger and more sus-
tained (within limits) until nervous stimulation ceases. As the ᭤ Define motor unit and muscle twitch, and describe the
Ca2ϩ pumps of the SR reclaim calcium ions from the cytosol events occurring during the three phases of a muscle twitch.
and troponin again changes shape, actin’s myosin-binding sites
are again covered by tropomyosin. The contraction ends, and ᭤ Explain how smooth, graded contractions of a skeletal
the muscle fiber relaxes. muscle are produced.

When the cycle is back where it started, the myosin head is in ᭤ Differentiate between isometric and isotonic contractions.
its upright high-energy configuration (see step 1 in Focus
Figure 9.12), ready to take another “step” and attach to an actin In its relaxed state, a muscle is soft and unimpressive, not what 9
site farther along the thin filament. This “walking” of the myosin you would expect of a prime mover of the body. However,
heads along the adjacent thin filaments during muscle shorten- within a few milliseconds, it can contract to become a hard elas-
ing is much like a centipede’s gait. The thin filaments cannot tic structure with dynamic characteristics that intrigue not only
slide backward as the cycle repeats again and again because some biologists but engineers and physicists as well.
myosin heads (“legs”) are always in contact with actin (the
“ground”). Contracting muscles routinely shorten by 30–35% of Before we consider muscle contraction on the organ level,
their total resting length, so each myosin cross bridge attaches let’s note a few principles of muscle mechanics.
and detaches many times during a single contraction. It is likely
that only half of the myosin heads of a thick filament are pulling 1. The principles governing contraction of a single muscle
at the same instant. The others are randomly seeking their next fiber and of a skeletal muscle consisting of a large number
binding site. of fibers are pretty much the same.

Except for the brief period following muscle cell excitation, 2. The force exerted by a contracting muscle on an object is
calcium ion concentrations in the cytosol are kept almost called muscle tension, and the opposing force exerted on
undetectably low. There is a reason for this: ATP is the cell’s en- the muscle by the weight of the object to be moved is
ergy source, and its hydrolysis yields inorganic phosphate (Pi). called the load.
Pi would combine with calcium ions to form hydroxyapatite
crystals, the stony-hard salts found in bone matrix, if calcium 3. A contracting muscle does not always shorten and move
ion concentrations were always high. Such calcified muscle cells the load. If muscle tension develops but the load is not
would die. moved, the contraction is called isometric (“same mea-
sure”), as when you try to lift a 2000-lb car. If the muscle
HOMEOSTATIC IMBALANCE tension developed overcomes the load and muscle shorten-
ing occurs, the contraction is isotonic (“same tension”),
Rigor mortis (death rigor) illustrates the fact that cross bridge as when you lift a 5-lb sack of sugar. We will describe these
detachment is ATP driven. Most muscles begin to stiffen 3 to major types of contraction in detail, but for now the im-
4 hours after death. Peak rigidity occurs at 12 hours and then portant thing to remember when reading the accompany-
gradually dissipates over the next 48 to 60 hours. Dying cells are ing graphs is that increasing muscle tension is measured for
unable to exclude calcium (which is in higher concentration in isometric contractions, whereas the amount of muscle short-
the extracellular fluid), and the calcium influx into muscle cells ening (distance in millimeters) is measured for isotonic
promotes formation of myosin cross bridges. Shortly after contractions.
breathing stops, ATP synthesis ceases, but ATP continues to be
consumed and cross bridge detachment is impossible. Actin 4. A skeletal muscle contracts with varying force and for dif-
and myosin become irreversibly cross-linked, producing the ferent periods of time in response to stimuli of varying fre-
stiffness of rigor mortis, which gradually disappears as muscle quencies and intensities. To understand how this occurs,
proteins break down after death. ■ we must look at the nerve-muscle functional unit called a
motor unit. This is our next topic.
CHECK YOUR UNDERSTANDING
The Motor Unit
6. What are the three structural components of a neuromuscu-
lar junction? Each muscle is served by at least one motor nerve, and each mo-
tor nerve contains axons (fibrous extensions) of up to hundreds
7. What is the final trigger for contraction? What is the initial of motor neurons. As an axon enters a muscle, it branches into
trigger? a number of terminals, each of which forms a neuromuscular
junction with a single muscle fiber. A motor unit consists of a
8. What prevents the filaments from sliding back to their motor neuron and all the muscle fibers it supplies (Figure 9.13).
original position each time a myosin cross bridge detaches When a motor neuron fires (transmits an action potential), all
from actin? the muscle fibers it innervates contract.

9. What would happen if a muscle fiber suddenly ran out of The number of muscle fibers per motor unit may be as high
ATP when sarcomeres had only partially contracted? as several hundred or as few as four. Muscles that exert fine con-
trol (such as those controlling the fingers and eyes) have small
For answers, see Appendix G. motor units. By contrast, large, weight-bearing muscles, whose
movements are less precise (such as the hip muscles), have large
motor units. The muscle fibers in a single motor unit are not







Chapter 9 Muscles and Muscle Tissue 293

Spinal cord

Axon terminals at Branching axon
neuromuscular junctions to motor unit

Motor Motor
unit 1 unit 2

Motor neuron Nerve
cell body Motor neuron
axon

Muscle

Muscle 9
fibers
(b) Branching axon terminals form
(a) Axons of motor neurons extend from the spinal cord to the muscle. There each axon divides neuromuscular junctions, one
into a number of axon terminals that form neuromuscular junctions with muscle fibers per muscle fiber (photomicro-
scattered throughout the muscle. graph 330ϫ).

Figure 9.13 A motor unit consists of a motor neuron and all the muscle fibers it
innervates. (See A Brief Atlas of the Human Body, Plate 30.)

clustered together but are spread throughout the muscle. As a 3. Period of relaxation. The period of contraction is followed
result, stimulation of a single motor unit causes a weak contrac- by the period of relaxation. This final phase, lasting
tion of the entire muscle. 10–100 ms, is initiated by reentry of Ca2ϩ into the SR. Be-
cause contractile force is declining, muscle tension de-
The Muscle Twitch creases to zero and the tracing returns to the baseline. If
the muscle shortened during contraction, it now returns
Muscle contraction is easily investigated in the laboratory using to its initial length. Notice that a muscle contracts faster
an isolated muscle. The muscle is attached to an apparatus that than it relaxes, as revealed by the asymmetric nature of the
produces a myogram, a graphic recording of contractile activ- myogram tracing.
ity. The line recording the activity is called a tracing.
As you can see in Figure 9.14b, twitch contractions of some
The response of a motor unit to a single action potential of muscles are rapid and brief, as with the muscles controlling eye
its motor neuron is called a muscle twitch. The muscle fibers movements. In contrast, the fibers of fleshy calf muscles (gas-
contract quickly and then relax. Every twitch myogram has trocnemius and soleus) contract more slowly and remain con-
three distinct phases (Figure 9.14a). tracted for much longer periods. These differences between
muscles reflect metabolic properties of the myofibrils and en-
1. Latent period. The latent period is the first few millisec- zyme variations.
onds following stimulation when excitation-contraction
coupling is occurring. During this period, muscle tension Graded Muscle Responses
is beginning to increase but no response is seen on the
myogram. Muscle twitches—like those single, jerky contractions provoked
in a laboratory—may result from certain neuromuscular prob-
2. Period of contraction. The period of contraction is when lems, but this is not the way our muscles normally operate. In-
cross bridges are active, from the onset to the peak of ten- stead, healthy muscle contractions are relatively smooth and
sion development, and the myogram tracing rises to a vary in strength as different demands are placed on them. These
peak. This period lasts 10–100 ms. If the tension (pull) be- variations, needed for proper control of skeletal movement, are
comes great enough to overcome the resistance of a load,
the muscle shortens.

294 UNIT 2 Covering, Support, and Movement of the Body

Latent Period of Period of Single stimulus single twitch
period contraction relaxation

Percentage of Tension (g) Contraction
maximum tension
Relaxation

0 300
Stimulus
0 20 40 60 80 100 120 140
100 200
Single Time (ms) Time (ms)

stimulus (a) A single stimulus is delivered. The muscle contracts
and relaxes.

(a) Myogram showing the three phases of an isometric twitch

Low stimulation frequency unfused (incomplete) tetanus

9 Latent period Tension (g)

Extraocular muscle (lateral rectus)

Gastrocnemius Partial relaxation

Percentage of Soleus
maximum tension
0 Stimuli

100 200 300
Time (ms)

0 40 80 120 160 200 (b) If another stimulus is applied before the muscle relaxes
completely, then more tension results. This is temporal
Time (ms) (or wave) summation and results in unfused (or incomplete)
tetanus.

Single

stimulus

(b) Comparison of the relative duration of twitch responses of High stimulation frequency fused (complete) tetanus
three muscles

Figure 9.14 The muscle twitch.

referred to as graded muscle responses. In general, muscle con- Tension (g)
traction can be graded in two ways: (1) by changing the fre-
quency of stimulation and (2) by changing the strength of Stimuli
stimulation. 0

Muscle Response to Changes in Stimulus Frequency The 100 200 300
nervous system achieves greater muscular force by increasing Time (ms)
the firing rate of motor neurons. For example, if two identical
stimuli (electrical shocks or nerve impulses) are delivered to a (c) At higher stimulus frequencies, there is no relaxation at all
muscle in rapid succession, the second twitch will be stronger between stimuli. This is fused (complete) tetanus.
than the first. On a myogram the second twitch will appear to
ride on the shoulders of the first (Figure 9.15b). This phenome- Figure 9.15 Muscle response to changes in stimulation
non, called temporal or wave summation, occurs because the frequency.
second contraction occurs before the muscle has completely re-
laxed. Because the muscle is already partially contracted when
the next stimulus arrives and more calcium is being squirted
into the cytosol to replace that being reclaimed by the SR,

Chapter 9 Muscles and Muscle Tissue 295

Stimulus strengthStimulus voltage infrequently, for example, when someone shows superhuman
strength by lifting a fallen tree limb off a companion.
Maximal
stimulus Vigorous muscle activity cannot continue indefinitely.
Prolonged tetanus inevitably leads to muscle fatigue, a situa-
Threshold stimulus tion in which the muscle is unable to contract and its tension
drops to zero.
1 2 3 4 5 6 7 8 9 10
Stimuli to nerve Muscle Response to Changes in Stimulus Strength Wave 9
summation contributes to contractile force, but its primary
Tension Proportion of motor units excited function is to produce smooth, continuous muscle contractions
by rapidly stimulating a specific number of muscle cells. The
Strength of muscle contraction force of contraction is controlled more precisely by recruitment,
Maximal contraction also called multiple motor unit summation.

Time (ms) In the laboratory, recruitment is achieved by delivering
shocks of increasing voltage to the muscle, calling more and
Figure 9.16 Relationship between stimulus intensity (graph more muscle fibers into play. Stimuli that produce no observ-
at top) and muscle tension (tracing below). Below threshold able contractions are called subthreshold stimuli. The stimulus
voltage, no muscle response is seen on the tracing (stimuli 1 and 2). at which the first observable contraction occurs is called the
Once threshold (3) is reached, increases in voltage excite (recruit) threshold stimulus (Figure 9.16). Beyond this point, the muscle
more and more motor units until the maximal stimulus is reached (7). contracts more and more vigorously as the stimulus strength is
Further increases in stimulus voltage produce no further increase in increased. The maximal stimulus is the strongest stimulus that
contractile strength. produces increased contractile force. It represents the point at
which all the muscle’s motor units are recruited. Increasing the
muscle tension produced during the second contraction causes stimulus intensity beyond the maximal stimulus does not pro-
more shortening than the first. In other words, the contractions duce a stronger contraction. In the body, the same phenomenon
are summed. (However, the refractory period is always hon- is caused by neural activation of an increasingly large number of
ored. Thus, if a second stimulus is delivered before repolariza- motor units serving the muscle.
tion is complete, no wave summation occurs.)
The recruitment process is not random. Instead it is dictated
If the stimulus strength is held constant and the muscle is by the size principle. In any muscle, motor units with the small-
stimulated at an increasingly faster rate, the relaxation time be- est muscle fibers are controlled by small, highly excitable motor
tween the twitches becomes shorter and shorter, the concentra- neurons, and these motor units tend to be activated first. As
tion of Ca2ϩ in the cytosol higher and higher, and the degree of motor units with larger and larger muscle fibers begin to be ex-
wave summation greater and greater, progressing to a sustained cited, contractile strength increases. The largest motor units,
but quivering contraction referred to as unfused or incomplete containing large, coarse muscle fibers, have as much as 50 times
tetanus (Figure 9.15b). the contractile force of the smallest ones. They are controlled by
the largest, least excitable (highest-threshold) neurons and are
Finally, as the stimulation frequency continues to increase, activated only when the most powerful contraction is necessary
muscle tension increases until a maximal tension is reached. At (Figure 9.17).
this point all evidence of muscle relaxation disappears and the
contractions fuse into a smooth, sustained contraction plateau The size principle is important because it allows the increases
called fused or complete tetanus (tetЈah-nus; tetan = rigid, in force during weak contractions (for example, those that
tense) (Figure 9.15c). (Note that this term is often confused maintain posture or slow movements) to occur in small steps,
with the bacterial disease called tetanus that causes severe invol- whereas gradations in muscle force are progressively greater
untary contractions.) In the real world, fused tetanus happens when large amounts of force are needed for vigorous activities
such as jumping or running. This principle explains how the
same hand that pats your cheek can deliver a stinging slap.

Although all the motor units of a muscle may be recruited si-
multaneously to produce an exceptionally strong contraction,
motor units are more commonly activated asynchronously in
the body. At a given instant, some are in tetanus (usually un-
fused tetanus) while others are resting and recovering. This
technique helps prolong a strong contraction by preventing or
delaying fatigue. It also explains how weak contractions pro-
moted by infrequent stimuli can remain smooth.

Muscle Tone

Skeletal muscles are described as voluntary, but even relaxed
muscles are almost always slightly contracted, a phenomenon

296 UNIT 2 Covering, Support, and Movement of the Body

Tension When you flex your elbow to raise this textbook to your shoul-
der, the biceps muscle in your arm is contracting concentrically.
Motor Motor Time When returning the book to the desktop, the isotonic contrac-
unit 1 unit 2 tion of the biceps is eccentric. Basically, eccentric contractions
recruited recruited Motor put the body in position to contract concentrically. All jumping
(small (medium unit 3 and throwing activities involve both types of contraction.
fibers) fibers) recruited
(large In isometric contractions (metric = measure), tension may
fibers) build to the muscle’s peak tension-producing capacity, but the
muscle neither shortens nor lengthens (Figure 9.18b). Isometric
Figure 9.17 The size principle of recruitment. Recruitment of contractions occur when a muscle attempts to move a load that
is greater than the force (tension) the muscle is able to develop—
motor neurons controlling skeletal muscle fibers is orderly—small, think of trying to lift a piano singlehandedly. Muscles contract
isometrically when they act primarily to maintain upright pos-
highly excitable motor neurons are generally recruited more readily ture or to hold joints in stationary positions while movements
occur at other joints.
9 than large, less excitable ones. This phenomenon is referred to as
the size principle. In weaker contractions, small motor units con- Let’s consider knee bends as an example. When the squat po-
sition is held for a few seconds, the quadriceps muscles of the
taining small-diameter muscle fibers are recruited. As contractile anterior thigh contract isometrically to hold the knee in the
flexed position. They also contract isometrically when we begin
strength increases, larger and larger motor units containing larger to rise to the upright position until their tension exceeds the
load (weight of the upper body). At that point muscle shorten-
numbers of increasingly larger-diameter muscle fibers are activated. ing (concentric contraction) begins. So the quadriceps contrac-
tile sequence for a deep knee bend from start to finish is (1) flex
Consequently, the contractions get stronger and stronger in a pre- knee (eccentric), (2) hold squat position (isometric), (3) extend
knee (isometric, then concentric). Of course, this list does not
dictable way. even begin to consider the isometric contractions of the poste-
rior thigh muscles or of the trunk muscles that maintain a rela-
called muscle tone. Muscle tone is due to spinal reflexes that tively erect trunk posture during the movement.
activate first one group of motor units and then another in
response to activation of stretch receptors in the muscles. Mus- Electrochemical and mechanical events occurring within a
cle tone does not produce active movements, but it keeps the muscle are identical in both isotonic and isometric contrac-
muscles firm, healthy, and ready to respond to stimulation. tions. However, the result is different. In isotonic contractions,
Skeletal muscle tone also helps stabilize joints and maintain the thin filaments are sliding. In isometric contractions, the
posture. cross bridges are generating force but are not moving the thin
filaments, so there is no change in the banding pattern from that
Isotonic and Isometric Contractions of the resting state. (You could say that they are “spinning their
wheels” on the same actin binding sites.)
As noted earlier, there are two main categories of contractions—
isotonic and isometric. In isotonic contractions (iso = same; ton CHECK YOUR UNDERSTANDING
= tension), muscle length changes and moves the load. Once
sufficient tension has developed to move the load, the tension 10. What is a motor unit?
remains relatively constant through the rest of the contractile 11. What is happening in the muscle during the latent period of
period (Figure 9.18a).
a twitch contraction?
Isotonic contractions come in two “flavors”—concentric and 12. Jay is competing in a chin-up competition. What type of mus-
eccentric. Concentric contractions are those in which the mus-
cle shortens and does work, such as picking up a book or kicking cle contractions are occurring in his biceps muscles immedi-
a ball. These contractions are probably more familiar. However, ately after he grabs the bar? As his body begins to move
eccentric contractions, in which the muscle generates force as it upward toward the bar? When his body begins to approach
lengthens, are equally important for coordination and purpose- the mat?
ful movements. Eccentric contractions occur in your calf mus-
cle, for example, as you walk up a steep hill. Eccentric For answers, see Appendix G.
contractions are about 50% more forceful than concentric ones
at the same load and more often cause delayed-onset muscle Muscle Metabolism
soreness. (Consider how your calf muscles feel the day after hik-
ing up that hill.) Just why this is so is unclear, but it may be that ᭤ Describe three ways in which ATP is regenerated during
the muscle stretching that occurs during such contractions skeletal muscle contraction.
causes microtears in the muscles.
᭤ Define oxygen deficit and muscle fatigue. List possible
Biceps curls provide a simple example of how concentric and causes of muscle fatigue.
eccentric contractions work together in our everyday activities.





Chapter 9 Muscles and Muscle Tissue 299

Short-duration exercise Prolonged-duration exercise

6 seconds 10 seconds 30–40 seconds End of exercise Hours

ATP stored in ATP is formed from Glycogen stored in muscles is broken down to glucose, ATP is generated by breakdown 9
muscles is creatine phosphate which is oxidized to generate ATP. of several nutrient energy fuels by
used first. and ADP. aerobic pathway. This pathway
uses oxygen released from myo-
globin or delivered in the blood by
hemoglobin. When it ends, the
oxygen deficit is paid back.

Figure 9.20 Comparison of energy sources used during short-duration exercise and
prolonged-duration exercise.

duces ATP about 21⁄2 times faster. For this reason, when large As exercise begins, muscle glycogen provides most of the fuel.
amounts of ATP are needed for moderate periods (30–40 sec- Shortly thereafter, bloodborne glucose, pyruvic acid from glycol-
onds) of strenuous muscle activity, glycolysis can provide most ysis, and free fatty acids are the major sources of fuels. After about
of the ATP needed as long as the required fuels and enzymes are 30 minutes, fatty acids become the major energy fuels. Aerobic
available. Together, stored ATP and CP and the glycolysis–lactic respiration provides a high yield of ATP (about 32 ATP per glu-
acid pathway can support strenuous muscle activity for nearly a cose), but it is slow because of its many steps and it requires con-
minute. tinuous delivery of oxygen and nutrient fuels to keep it going.

Although anaerobic glycolysis readily fuels spurts of vigor- Energy Systems Used During Sports Activities Which path-
ous exercise, it has shortcomings. Huge amounts of glucose are ways predominate during exercise? As long as it has enough
used to produce relatively small harvests of ATP, and the accu- oxygen, a muscle cell will form ATP by the aerobic pathway.
mulating lactic acid is partially responsible for muscle soreness When ATP demands are within the capacity of the aerobic path-
during intense exercise. way, light to moderate muscular activity can continue for sev-
eral hours in well-conditioned individuals (Figure 9.20).
Aerobic Respiration (Figure 9.19c) During rest and light to However, when exercise demands begin to exceed the ability of
moderate exercise, even if prolonged, 95% of the ATP used the muscle cells to carry out the necessary reactions quickly
for muscle activity comes from aerobic respiration. Aerobic enough, glycolysis begins to contribute more and more of the
respiration occurs in the mitochondria, requires oxygen, and total ATP generated. The length of time a muscle can continue
involves a sequence of chemical reactions in which the bonds of to contract using aerobic pathways is called aerobic endurance,
fuel molecules are broken and the energy released is used to and the point at which muscle metabolism converts to anaero-
make ATP. bic glycolysis is called anaerobic threshold.

During aerobic respiration, which includes glycolysis and the Exercise physiologists have been able to estimate the relative
reactions that take place in the mitochondria, glucose is broken importance of each energy-producing system to athletic per-
down entirely, yielding water, carbon dioxide, and large formance. Activities that require a surge of power but last only a
amounts of ATP as the final products. few seconds, such as weight lifting, diving, and sprinting, rely
entirely on ATP and CP stores. The more on-and-off or burst-
Glucose ϩ oxygen n carbon dioxide ϩ water ϩ ATP like activities of tennis, soccer, and a 100-meter swim appear to
be fueled almost entirely by anaerobic glycolysis (Figure 9.20).
The carbon dioxide released diffuses out of the muscle tissue
into the blood and is removed from the body by the lungs.

300 UNIT 2 Covering, Support, and Movement of the Body

Prolonged activities such as marathon runs and jogging, where vert any lactic acid persisting in blood to glucose or glycogen.
endurance rather than power is the goal, depend mainly on aer- During anaerobic muscle contraction, all of these oxygen-
obic respiration. Levels of CP and ATP don’t change much dur- requiring activities occur more slowly and are (at least partially)
ing prolonged exercise because ATP is generated at the same rate deferred until oxygen is again available. For this reason, we say an
as it is used—a “pay as you go” system. Compared to anaerobic oxygen deficit is incurred, which must be repaid. Oxygen deficit
energy production, aerobic generation of ATP is relatively slow, is defined as the extra amount of oxygen that the body must take
but the ATP harvest is enormous. in for these restorative processes. It represents the difference be-
tween the amount of oxygen needed for totally aerobic muscle
Muscle Fatigue activity and the amount actually used. All anaerobic sources of
ATP used during muscle activity contribute to this deficit.
Muscle fatigue is a state of physiological inability to contract even
though the muscle still may be receiving stimuli. Although Heat Production During Muscle Activity
many factors appear to contribute to fatigue, its specific causes Only about 40% of the energy released during muscle contrac-
are not fully understood. Most experimental evidence indicates tion is converted to useful work (still, this percentage is signifi-
that fatigue is due to a problem in excitation-contraction cou- cantly higher than that of many mechanical devices). The rest is
pling or, in rare cases, problems at the neuromuscular junction. given off as heat, which has to be dealt with if body homeostasis
Availability of ATP declines during contraction, but normally it is to be maintained. When you exercise vigorously, you start to
is unusual for a muscle to totally run out of ATP. So, ATP is not feel hot as your blood is warmed by the liberated heat. Like a
a fatigue-producing factor in moderate exercise. A total lack of car’s cooling system that dissipates heat, heat buildup in the
9 ATP results in contractures, states of continuous contraction body is prevented from reaching dangerous levels by several
because the cross bridges are unable to detach (not unlike what homeostatic processes, including sweating and radiation of heat
happens in rigor mortis). Writer’s cramp is a familiar example from the skin surface. Shivering represents the opposite side of
of temporary contractures. homeostatic balance, in which muscle contractions are used to
produce more heat.
Several ionic imbalances contribute to muscle fatigue. As ac-
tion potentials are transmitted, potassium is lost from the mus- CHECK YOUR UNDERSTANDING
cle cells, and the Naϩ-Kϩ pumps are inadequate to reverse the
ionic imbalances quickly, so Kϩ accumulates in the fluids of the 13. When Eric returned from jogging, he was breathing heavily,
T tubules. This ionic change disturbs the membrane potential sweating profusely, and complained that his legs ached and
of the muscle cells and halts Ca2ϩ release from the SR. Theoret- felt weak. He wife poured him a sports drink and urged him
ically, in short-duration exercise, an accumulation of inorganic to take it easy until he could “catch his breath.” On the basis
phosphate (Pi) from CP and ATP breakdown may interfere with of what you have learned about muscle energy metabolism,
calcium release from the SR or alternatively with the release of respond to the following questions: Why is Eric breathing
Pi from myosin and thus hamper myosin’s power strokes. Lactic heavily? What ATP-generating pathway have his working
acid has long been assumed to be a major cause of fatigue, but it muscles been using that leads to such breathlessness? What
seems to be more important in provoking central (psychologi- metabolic products might account for his sore muscles and
cal) fatigue (in which the muscles are still willing to “go” but we his feeling of muscle weakness?
feel too tired to continue the activity) than physiological fatigue.
Excessive intracellular accumulation of lactic acid (which causes For answers, see Appendix G.
the muscles to ache) raises the concentration of Hϩ and alters
contractile proteins; however, pH is normally regulated within Force of Muscle Contraction
normal limits in all but the greatest degree of exertion. Addi-
tionally, lactic acid has recently been shown to counteract high ᭤ Describe factors that influence the force, velocity, and
Kϩ levels which do lead to muscle fatigue (as noted above). duration of skeletal muscle contraction.

In general, intense exercise of short duration produces fa- ᭤ Describe three types of skeletal muscle fibers and explain
tigue rapidly via ionic disturbances that alter E-C coupling, but the relative value of each type.
recovery is also rapid. In contrast to short-duration exercise, the
slow-developing fatigue of prolonged low-intensity exercise The force of muscle contraction is affected by (1) the number
may require several hours for complete recovery. It appears that of muscle fibers stimulated, (2) the relative size of the fibers,
this type of exercise damages the SR, interfering with Ca2ϩ reg- (3) the frequency of stimulation, and (4) the degree of muscle
ulation and release, and therefore with muscle activation. stretch (Figure 9.21). Let’s briefly examine the role of each of
these factors.
Oxygen Deficit
Number of Muscle Fibers Stimulated
Whether or not fatigue occurs, vigorous exercise causes a mus- As already discussed, the more motor units that are recruited,
cle’s chemistry to change dramatically. For a muscle to return to the greater the muscle force.
its resting state, its oxygen reserves must be replenished, the ac-
cumulated lactic acid must be reconverted to pyruvic acid, glyco-
gen stores must be replaced, and ATP and creatine phosphate
reserves must be resynthesized. Additionally, the liver must con-









Chapter 9 Muscles and Muscle Tissue 305

Longitudinal layer of smooth
muscle (shows smooth muscle fibers
in cross section)

Small intestine

Mucosa

(a) (b) Cross section of the intestine showing Circular layer of smooth muscle 9
the smooth muscle layers (one circular (shows longitudinal views of smooth
and the other longitudinal) running at muscle fibers)
right angles to each other.

Figure 9.26 Arrangement of smooth muscle in the walls of hollow organs.

HOMEOSTATIC IMBALANCE smooth muscle. The chemical and mechanical events of con-
traction are essentially the same in all muscle tissues, but
To remain healthy, muscles must be active. Complete immobi- smooth muscle is distinctive in several ways that are summa-
lization due to enforced bed rest or loss of neural stimulation re- rized in Table 9.3.
sults in disuse atrophy (degeneration and loss of mass), which
begins almost as soon as the muscles are immobilized. Under Microscopic Structure of Smooth Muscle Fibers
such conditions, muscle strength can decrease at the rate of
5% per day! Smooth muscle fibers are spindle-shaped cells of variable size,
each with one centrally located nucleus (Figure 9.26b). Typi-
As noted earlier, even at rest, muscles receive weak intermit- cally, they have a diameter of 5–10 µm and are 30–200 µm long.
tent stimuli from the nervous system. When totally deprived of Skeletal muscle fibers are up to 10 times wider and thousands of
neural stimulation, a paralyzed muscle may atrophy to one- times longer.
quarter of its initial size. Lost muscle tissue is replaced by fibrous
connective tissue, making muscle rehabilitation impossible. ■ Smooth muscle lacks the coarse connective tissue sheaths
seen in skeletal muscle. However, a small amount of fine con-
CHECK YOUR UNDERSTANDING nective tissue (endomysium), secreted by the smooth muscles
themselves and containing blood vessels and nerves, is found
16. Relative to their effect on muscle size and function, how do between smooth muscle fibers.
aerobic and anaerobic exercise differ?
Most smooth muscle is organized into sheets of closely ap-
For answers, see Appendix G. posed fibers. These sheets occur in the walls of all but the small-
est blood vessels and in the walls of hollow organs of the
Smooth Muscle respiratory, digestive, urinary, and reproductive tracts. In most
cases, two sheets of smooth muscle are present, with their fibers
᭤ Compare the gross and microscopic anatomy of smooth oriented at right angles to each other, as in the intestine (Fig-
muscle cells to that of skeletal muscle cells. ure 9.26). In the longitudinal layer, the muscle fibers run parallel
to the long axis of the organ. Consequently, when the muscle
᭤ Compare and contrast the contractile mechanisms and the contracts, the organ dilates and shortens. In the circular layer,
means of activation of skeletal and smooth muscles. the fibers run around the circumference of the organ. Contrac-
tion of this layer constricts the lumen (cavity) of the organ and
᭤ Distinguish between single-unit and multiunit smooth mus- causes the organ to elongate.
cle structurally and functionally.
The alternating contraction and relaxation of these opposing
Except for the heart, which is made of cardiac muscle, the mus- layers mixes substances in the lumen and squeezes them
cle in the walls of all the body’s hollow organs is almost entirely through the organ’s internal pathway. This propulsive action is

306 UNIT 2 Covering, Support, and Movement of the Body

Intermediate Caveolae Gap junctions
filament
Varicosities

Nucleus Dense bodies

Autonomic Smooth (a) Relaxed smooth muscle fiber (note that adjacent fibers
nerve fibers muscle are connected by gap junctions)
innervate cell
most smooth
muscle fibers. Nucleus

Dense bodies

Synaptic Mitochondrion Varicosities release (b) Contracted smooth muscle fiber

vesicles their neurotransmitters Figure 9.28 Intermediate filaments and dense bodies of
smooth muscle fibers harness the pull generated by myosin
into a wide synaptic cross bridges. Intermediate filaments attach to dense bodies
throughout the sarcoplasm.
9 cleft (a diffuse junction).
There are no striations, as the name smooth muscle indicates,
Figure 9.27 Innervation of smooth muscle. and therefore no sarcomeres. Smooth muscle fibers do contain
interdigitating thick and thin filaments, but they are much
called peristalsis (perЉ˘ı-stalЈsis; “around contraction”). Con- longer than those in skeletal muscle, and the type of myosin
traction of smooth muscle in the rectum, urinary bladder, and contained differs in smooth muscle. The proportion and orga-
uterus helps those organs to expel their contents. Smooth mus- nization of the myofilaments are also different:
cle contraction also accounts for the constricted breathing of
asthma and for stomach cramps. 1. Thick filaments are fewer but have myosin heads along
their entire length. The ratio of thick to thin filaments is
Smooth muscle lacks the highly structured, specific neuro- much lower in smooth muscle than in skeletal muscle
muscular junctions of skeletal muscle. Instead, the innervating (1:13 compared to 1:2). However, thick filaments of
nerve fibers, which are part of the autonomic (involuntary) smooth muscle contain actin-gripping myosin heads
nervous system, have numerous bulbous swellings, called along their entire length, a feature that allows smooth mus-
varicosities (Figure 9.27). The varicosities release neurotrans- cle to be as powerful as a skeletal muscle of the same size.
mitter into a wide synaptic cleft in the general area of the
smooth muscle cells. Such junctions are called diffuse 2. No troponin complex in thin filaments. As opposed to
junctions. Comparing the specificity of neural input to skeletal skeletal muscle which has calcium-binding troponin on
and smooth muscles, you could say that skeletal muscle gets pri- the thin filaments, no troponin complex is present in
ority mail while smooth muscle gets bulk mailings. smooth muscle. Instead, a protein called calmodulin acts as
the calcium-binding site.
The sarcoplasmic reticulum of smooth muscle fibers is much
less developed than that of skeletal muscle and lacks a specific 3. Thick and thin filaments arranged diagonally. Bundles of
pattern relative to the myofilaments. Some SR tubules of contractile proteins crisscross within the smooth muscle
smooth muscle touch the sarcolemma at several sites, forming cell so they spiral down the long axis of the cell like the
what resembles half-triads that may couple the action potential stripes on a barber pole. Because of this diagonal arrange-
to calcium release from the SR. T tubules are notably absent, but ment, the smooth muscle cells contract in a twisting way
the sarcolemma of the smooth muscle fiber has multiple so that they look like tiny corkscrews (Figure 9.28b).
caveolae, pouchlike infoldings that sequester bits of extracellu-
lar fluid containing a high concentration of Ca2ϩ close to the 4. Intermediate filament–dense body network. Smooth
membrane (Figure 9.28a). Consequently, when calcium chan- muscle fibers contain a lattice-like arrangement of non-
nels in the caveolae open, Ca2ϩ influx occurs rapidly. Although contractile intermediate filaments that resist tension. They
the SR does release some of the calcium that triggers contrac- attach at regular intervals to cytoplasmic structures called
tion, most enters through calcium channels directly from the dense bodies (Figure 9.28). The dense bodies, which are
extracellular space. Contraction ends when calcium is actively also tethered to the sarcolemma, act as anchoring points
transported into the SR and out of the cell. This situation is for thin filaments and therefore correspond to Z discs of
quite different from what we see in skeletal muscle, which does skeletal muscle. The intermediate filament–dense body
not depend on extracellular Ca2ϩ for excitation-contraction network forms a strong, cable-like intracellular cytoskeleton
coupling. that harnesses the pull generated by the sliding of the thick

Chapter 9 Muscles and Muscle Tissue 307

and thin filaments. During contraction, areas of the sar- Extracellular fluid (ECF) Plasma membrane
colemma between the dense bodies bulge outward, giving Ca2+
the cell a puffy appearance, as in Figure 9.28b. Dense bod-
ies at the sarcolemma surface also bind the muscle cell to Cytoplasm Ca2+
the connective tissue fibers outside the cell (endomysium)
and to adjacent cells. This arrangement transmits the 1 Calcium ions (Ca2+) Sarcoplasmic 9
pulling force to the surrounding connective tissue and enter the cytosol from reticulum
partly accounts for the synchronous contraction of most the ECF via voltage-
smooth muscle. dependent or voltage- Ca2+
independent Ca2+
Contraction of Smooth Muscle channels, or from Activated calmodulin
the scant SR.
Mechanism of Contraction
2 Ca2+ binds to and
In most cases, adjacent smooth muscle fibers exhibit slow, syn- activates calmodulin.
chronized contractions, the whole sheet responding to a stimu-
lus in unison. This synchronization reflects electrical coupling of Inactive calmodulin
smooth muscle cells by gap junctions, specialized cell connec-
tions described in Chapter 3. Skeletal muscle fibers are electri- 3 Activated calmodulin Activated kinase
cally isolated from one another, each stimulated to contract by its activates the myosin
own neuromuscular junction. By contrast, gap junctions allow light chain kinase
smooth muscles to transmit action potentials from fiber to fiber. enzymes.

Some smooth muscle fibers in the stomach and small intes- Inactive kinase
tine are pacemaker cells and, once excited, they act as “drum-
mers” to set the contractile pace for the entire muscle sheet. 4 The activated kinase enzymes ATP
Additionally, these pacemakers have fluctuating membrane po- catalyze transfer of phosphate ADP
tentials and are self-excitatory, that is, they depolarize sponta- to myosin, activating the myosin
neously in the absence of external stimuli. However, both the ATPases.
rate and the intensity of smooth muscle contraction may be
modified by neural and chemical stimuli. Inactive Pi
myosin molecule Pi
Contraction in smooth muscle is like that in skeletal muscle
in the following ways: (1) actin and myosin interact by the slid- Activated (phosphorylated)
ing filament mechanism; (2) the final trigger for contraction is a myosin molecule
rise in the intracellular calcium ion level; and (3) the sliding
process is energized by ATP. 5 Activated myosin forms cross
bridges with actin of the thin
During excitation-contraction coupling, Ca2ϩ is released by filaments and shortening begins.
the tubules of the SR, but, as mentioned above, it also moves
into the cell via membrane channels from the extracellular Thin
space. By binding to troponin, calcium ions activate myosin in filament
all striated muscle types, but in smooth muscle, they activate
myosin by interacting with a regulatory molecule called Thick
calmodulin, a cytoplasmic calcium-binding protein. Calmod- filament
ulin, in turn, interacts with a kinase enzyme called myosin
kinase or myosin light chain kinase which phosphorylates the Figure 9.29 Sequence of events in excitation-contraction
myosin, activating it. This sequence of events is depicted in coupling of smooth muscle.
Figure 9.29. (Note that this is just one pathway of smooth mus-
cle activation. There are others. For example, in some smooth
muscles, regulatory proteins associated with actin appear to
play a role.)

As in skeletal muscle, smooth muscle relaxes when intracel-
lular Ca2ϩ levels drop, but getting muscle to cease its contractile
activity is quite a bit more complex in smooth muscle then in
skeletal muscle. Events known to be involved include calcium
detachment from calmodulin, active transport of Ca2ϩ into the
SR and the extracellular fluid, and dephosphorylation of
myosin by a phosphorylase enzyme, which reduces the activity
of the myosin ATPases.







Chapter 9 Muscles and Muscle Tissue 311
Satellite cell
Embryonic Myoblasts Myotube
mesoderm cells (immature
multinucleate
muscle fiber)

1 Embryonic 2 Several 3 Myotube Mature skeletal
mesoderm cells myoblasts fuse matures into muscle fiber
undergo cell division together to form skeletal muscle
(to increase number) a myotube. fiber.
and enlarge.

Figure 9.30 Formation of a multinucleate skeletal muscle fiber by fusion of myoblasts.

muscle fibers can divide to increase their numbers, that is, they 1. Consists of muscle fibers that are structurally independent 9
undergo hyperplasia. One example is the response of the uterus of one another
to estrogen. At puberty, girls’ plasma estrogen levels rise. As estro-
gen binds to uterine smooth muscle receptors, it stimulates the 2. Is richly supplied with nerve endings, each of which forms
synthesis of more uterine smooth muscle, causing the uterus to a motor unit with a number of muscle fibers
grow to adult size. During pregnancy, high blood levels of estro-
gen stimulate uterine hyperplasia to accommodate the grow- 3. Responds to neural stimulation with graded contractions
ing fetus. that involve recruitment

Types of Smooth Muscle However, while skeletal muscle is served by the somatic (volun-
tary) division of the nervous system, multiunit smooth muscle
The smooth muscle in different body organs varies substantially (like single-unit smooth muscle) is innervated by the auto-
in its (1) fiber arrangement and organization, (2) innervation, nomic (involuntary) division and is also responsive to hor-
and (3) responsiveness to various stimuli. For simplicity, how- monal controls.
ever, smooth muscle is usually categorized into two major types:
single-unit and multiunit. CHECK YOUR UNDERSTANDING

Single-Unit Smooth Muscle 17. Compare the structure of skeletal muscle fibers to that of
smooth muscle fibers.
Single-unit smooth muscle, commonly called visceral muscle
because it is in the walls of all hollow organs except the heart, 18. Calcium is the trigger for contraction of all muscle types.
is far more common. All the smooth muscle characteristics How does its binding site differ in skeletal and smooth mus-
described so far pertain to single-unit smooth muscle. For ex- cle fibers?
ample, the cells of single-unit smooth muscle
19. How does the stress-relaxation response suit the role of
1. Are arranged in opposing (longitudinal and circular) smooth muscle in hollow organs?
sheets
For answers, see Appendix G.
2. Are innervated by ANS varicosities and often exhibit
rhythmic spontaneous action potentials Developmental Aspects of Muscles

3. Are electrically coupled by gap junctions and so contract ᭤ Describe embryonic development of muscle tissues and the
as a unit (for this reason recruitment is not an option in changes that occur in skeletal muscles with age.
smooth muscle)
With rare exceptions, all three types of muscle tissue develop
4. Respond to various chemical stimuli from embryonic mesoderm cells called myoblasts. In forming
skeletal muscle tissue several myoblasts fuse to form multinu-
Multiunit Smooth Muscle clear myotubes (Figure 9.30). This process is guided by the in-
tegrins (cell adhesion proteins) in the myoblast membranes.
The smooth muscles in the large airways to the lungs and in Soon functional sarcomeres are present, and skeletal muscle
large arteries, the arrector pili muscles attached to hair follicles, fibers are contracting by week 7 when the embryo is only about
and the internal eye muscles that adjust pupil size and allow the 2.5 cm (1 inch long).
eye to focus visually are all examples of multiunit smooth
muscle. Initially, ACh receptors “sprout” over the entire surface of the
developing myoblasts. As spinal nerves invade the muscle masses,
In contrast to what we see in single-unit muscle, gap junc- the nerve endings target individual myoblasts and release the
tions are rare, and spontaneous synchronous depolarizations growth factor agrin. This chemical activates a muscle kinase
are infrequent. Like skeletal muscle, multiunit smooth muscle (MuSK), which stimulates clustering and maintenance of ACh
receptors at the newly forming neuromuscular junction in each

312 UNIT 2 Covering, Support, and Movement of the Body

muscle fiber. Then, the nerve endings provide an independent connective tissue deposit, but the muscle fibers atrophy and
degenerate.
chemical signal that causes elimination of the receptor sites not
The most common and serious form is Duchenne muscular
innervated and not stabilized by agrin. dystrophy (DMD), which is inherited as a sex-linked recessive
disease: Females carry and transmit the abnormal gene, but it is
Electrical activity in the neurons serving the muscle fibers expressed almost exclusively in males (one in every 3500 births).
This tragic disease is usually diagnosed when the boy is between
also plays a critical role in muscle fiber maturation. As the mus- 2 and 7 years old. Active, normal-appearing children become
clumsy and fall frequently as their skeletal muscles weaken. The
cle fibers are brought under the control of the somatic nervous disease progresses relentlessly from the extremities upward, fi-
nally affecting the head and chest muscles and cardiac muscle of
system, the number of fast and slow contractile fiber types is the heart. Victims rarely live beyond their early 20s, dying of res-
piratory failure.
determined.
Recent research has pinned down the cause of DMD: The
Myoblasts producing cardiac and smooth muscle cells do not diseased muscle fibers lack dystrophin, a cytoplasmic protein
that links the cytoskeleton to the extracellular matrix and, like
fuse. However, both develop gap junctions at a very early em- a girder, helps stabilize the sarcolemma. The fragile sar-
colemma of DMD patients tears during contraction, allowing
bryonic stage. Cardiac muscle is pumping blood just 3 weeks entry of excess Ca2ϩ. The deranged calcium homeostasis dam-
ages the contractile fibers which then break down, and inflam-
after fertilization. matory cells (macrophages and lymphocytes) accumulate in
the surrounding connective tissue. As the regenerative capacity
Specialized skeletal and cardiac muscle cells stop dividing of the muscle is lost, and damaged cells undergo apoptosis,
muscle mass drops.
early on but retain the ability to lengthen and thicken in a grow-
There is still no cure for DMD, and thus far the only medica-
ing child and to hypertrophy in adults. However, myoblast-like tion that has improved muscle strength and function is the
steroid prednisone. One initially promising technique,
cells associated with skeletal muscle, called satellite cells (Fig- myoblast transfer therapy, involves injecting diseased muscle
with healthy myoblast cells that fuse with the unhealthy ones.
ure 9.30), help repair injured fibers and allow very limited re- The idea is that the normal gene provided would allow the fiber
to produce dystrophin and so to grow normally. The therapy
generation of dead skeletal muscle fibers. Cardiac muscle was has shown some success in mice, but human trials have been
disappointing. The large size of the dystrophin gene and of hu-
9 thought to have no regenerative capability whatsoever, but re- man muscles presents a huge challenge to that therapy. Two
cent studies suggest that cardiac cells do divide at a modest rate. newer experimental therapies have each produced striking re-
versals of disease symptoms in dystrophic animal models. One
Nonetheless, injured heart muscle is repaired mostly by scar tis- is injection of adeno-associated viruses carrying pared-down
microdystrophin genes. The second is infusion into the blood-
sue. Smooth muscles are able to regenerate throughout life. stream of dystrophic mesangioblasts (stem cells harvested
from blood vessels) corrected by inserting microdystrophin
At birth, a baby’s movements are uncoordinated and largely genes. A different approach being tested is coaxing dystrophic
muscles to produce more utrophin, a similar protein present in
reflexive. Muscular development reflects the level of neuro- low amounts in adults but at much higher levels in fetal mus-
cles. In mice at least, utrophin can compensate for dystrophin
muscular coordination, which develops in a head-to-toe and deficiency. ■

proximal-to-distal direction. In other words, a baby can lift its As we age, the amount of connective tissue in our skeletal
muscles increases, the number of muscle fibers decreases, and
head before it can walk, and gross movements precede fine the muscles become stringier, or more sinewy. By the age of 30,
even in healthy people, a gradual loss of muscle mass, called
ones. All through childhood, our control of our skeletal mus- sarcopenia (sar-co-peЈne-ah), begins to occur as muscle pro-
teins start to degrade more rapidly than they can be replaced.
cles becomes more and more sophisticated. By midadoles- Just why this happens is still a question, but apparently the same
regulatory molecules (transcription factors, enzymes, hor-
cence, we reach the peak of our natural neural control of mones, and others) that promote muscle growth also oversee
this type of muscle atrophy. Because skeletal muscles form
muscles, and can either accept that level of development or im- so much of the body mass, body weight and muscle strength

prove it by athletic or other types of training. (Text continues on p. 316.)

A frequently asked question is whether the difference in

strength between women and men has a biological basis. It does.

Individuals vary, but on average, women’s skeletal muscles make

up approximately 36% of body mass, whereas men’s account for

about 42%. Men’s greater muscular development is due primar-

ily to the effects of testosterone on skeletal muscle, not to the

effects of exercise. Body strength per unit muscle mass, however,

is the same in both sexes. Strenuous muscle exercise causes

more muscle enlargement in males than in females, again be-

cause of the influence of testosterone. Some athletes take large

doses of synthetic male sex hormones (“steroids”) to increase

their muscle mass. This illegal and physiologically dangerous

practice is discussed in A Closer Look, opposite.

Because of its rich blood supply, skeletal muscle is amazingly

resistant to infection throughout life. Given good nutrition and

moderate exercise, relatively few problems afflict skeletal mus-

cles. However, muscular dystrophy, the world’s most common

genetic disorder, is a serious condition that deserves more than

a passing mention.

HOMEOSTATIC IMBALANCE

The term muscular dystrophy refers to a group of inherited
muscle-destroying diseases that generally appear during child-
hood. The affected muscles initially enlarge due to fat and