2.

Muscle physiology
2.1. How eskeletal muscles produce movements
2.2. Muscle Structure
2.3. Muscle Contraction

José A. Lorente, MD
josloren@ing.uc3m.es
Bioengineering Dept.
Universidad Carlos III de Madrid
Servicio de Medicina Intensiva, Hospital Universitario
de Getafe 1
 2.2. Muscle Structure

José A. Lorente, MD
josloren@ing.uc3m.es
Bioengineering Dept.
Universidad Carlos III de Madrid
Servicio de Medicina Intensiva, Hospital Universitario
de Getafe 2
 Three types of muscular tissue

Striated Smooth muscle tissue

• Alternating light and dark protein bands • Located in the walls of hollow internal structures
(striations) when the tissue is examined with a (e.g., blood vessels, airways, and most organs in the
microscope. abdominopelvic cavity), and in the skin (hair
• Voluntary movements. follicles).
• Activity is consciously controlled by neurons, • Lacks the striations.
part of the somatic (voluntary) division of the • It is usually involuntary.
nervous system. • Some smooth muscle tissue (e.g., in the GI tract),
• Most skeletal muscles also are controlled has autorhythmicity (peristalsis).
subconsciously to some extent (e.g., breathing). • Regulated by neurons (from the ANS) and by
Cardiac hormones (as cardiac muscle).
• Also striated.
• Its action is involuntary.
• Autorhythmicity and contractility.
• The heart beats because it has a pacemaker
(autorhythmicity).
• Regulated by
• Neurons that are part of the autonomic
(involuntary) division of the nervous
system.
• Hormones released by endocrine glands.
 Properties of muscular tissue
1. Electrical excitability
• A property of both muscle and neurons.
• The ability to respond to certain stimuli by
producing electrical signals called action
potentials (impulses).
• Action potentials in muscles are referred to as
muscle action potentials; those in nerve cells are
called nerve action potentials.
• Two main types of stimuli trigger action
potentials:
• Autorhythmic: electrical signals arising in the
muscular tissue itself, as in the heart’s
pacemaker.
• Chemical stimuli: such as
• neurotransmitters released by neurons,
• hormones distributed by the blood, or
• local changes in physiological
conditions.
2. Extensibility
• The ability of muscular tissue to stretch.
• The connective tissue within the muscle limits the
range of extensibility.
3. Contractility
• The ability of muscular tissue to contract forcefully
when stimulated by an action potential.
• When a skeletal muscle contracts, it generates
tension (force of contraction) while pulling on its
attachment points.
• Contraction may result in
• Change in tension without shortening
(isometric)
• the muscle develops tension (force of
contraction) but does not shorten.
• e.g., holding this book in an outstretched
hand.
• Shortening without change in tension (isotonic)
• the tension generated is great enough to
overcome the load (resistance) of the
object being moved so the muscle shortens
and movement occurs.
• e.g., lifting a book off a table.
4. Elasticity
• The ability of muscular tissue to return to its
original length and shape after contraction or
extension.
TISSUE

etal muscle and its connective tissue coverings.

Structure of muscular tissue
of individual muscle fibers (cells) bundled into fascicles and surrounded by three connective
nsions of the fascia.

Periosteum
Connective Tissue Components
Tendon
Connective tissue surrounds and protects muscular tissue.
Subcutaneous layer or hypodermis
Epimysium

Bone Belly of
• Separates muscle from skin is composed of areolar
skeletal muscle
Perimysium
connective tissue and adipose tissue.
Epimysium • It provides a pathway for nerves, blood vessels, and
lymphatic vessels to enter and exit muscles.
Fascicle
• The adipose tissue of the subcutaneous layer stores
Perimysium most of the body’s triglycerides, serves as an
Muscle
fiber (cell)
insulating layer that reduces heat loss, and protects
Myofibril muscles from physical trauma.
Endomysium
Perimysium Epimysium
Fascicle Somatic
motor neuron
Blood capillary
• The outermost layer of dense, irregular connective
Endomysium tissue, encircling the entire muscle.
Nucleus

Muscle fiber Perimysium

Striations
• A layer of dense, irregular connective tissue,
Transverse sections
Sarcoplasm
• Surrounding groups of 10-100 or more bers.
Sarcolemma
S • Separating those groups of 10 to 100 muscle bers
Myofibril
into bundles called fascicles.
n the body. Filament
• Many fascicles can be seen with the naked eye.
Components of a skeletal muscle

rounds groups of muscle fibers, separating them into fascicles?

• They give a cut of meat its characteristic “grain”.
• If you tear a piece of meat, it rips apart along the
fascicles.
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TISSUE

etal muscle and its connective tissue coverings.

Structure of muscular tissue
of individual muscle fibers (cells) bundled into fascicles and surrounded by three connective
nsions of the fascia.

Periosteum
Connective Tissue Components
Tendon
Endomysium
Epimysium • It penetrates the interior of each fascicle and separates
Bone Belly of individual muscle bers from one another.
skeletal muscle
Perimysium
• The endomysium is mostly reticular bers.
Epimysium

Epimysium, perimysium, and endomysium

Fascicle

• all are continuous with the connective tissue that

Perimysium attaches skeletal muscle to other structures, such as bone
Muscle
fiber (cell) or another muscle.
Myofibril

Endomysium • e.g. all three connective tissue layers may extend beyond
Perimysium
Fascicle Somatic the muscle bers to form a ropelike tendon that attaches
motor neuron
Blood capillary a muscle to the periosteum of a bone.
Endomysium
Nucleus
• e.g., the calcaneal (Achilles) tendon of the
Muscle fiber
gastrocnemius (calf) muscle, which attaches the
Striations
muscle to the calcaneus (heel bone).
Sarcoplasm
Transverse sections
Sarcolemma
S
Myofibril

n the body. Filament

Components of a skeletal muscle

rounds groups of muscle fibers, separating them into fascicles?

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Levels of Organization within a Skeletal Muscle
LEVEL DESCRIPTION

Skeletal muscle Organ made up of fascicles that contain muscle fibers (cells), blood
vessels, and nerves; wrapped in epimysium.
Tendon

Bone (covered by Epimysium

periosteum)
Skeletal muscle
Epimysium
Fascicle

Fascicle Bundle of muscle fibers wrapped in perimysium.

Fascicle Perimysium

Muscle
fiber

Muscle fiber (cell)

Long cylindrical cell covered by endomysium and sarcolemma; contains
Sarcoplasmic reticulum sarcoplasm, myofibrils, many peripherally located nuclei, mitochondria,
Sarcolemma transverse tubules, sarcoplasmic reticulum, and terminal cisterns. The fiber
Muscle has a striated appearance.
Myofibril
fiber
Sarcoplasm

Nucleus
Transverse
tubule
Terminal
cisterns
Mitochondrion
Myofibril Threadlike contractile elements within sarcoplasm of muscle fiber that
Thick Thin extend entire length of fiber; composed of filaments.
Z disc filament filament

Sarcomere
Filaments (myofilaments) Contractile proteins within myofibrils that are of two types: thick filaments
Thin filament composed of myosin and thin filaments composed of actin, tropomyosin,
Z disc Thick filament Z disc and troponin; sliding of thin filaments past thick filaments produces
muscle shortening.

Sarcomere
332 CHAPTER 10 • MUSCULAR TISSUE

Microscopic Anatomy of a Skeletal Muscle Fiber

Figure 10.2 Microscopic organization of skeletal muscle. (a) During embryonic development, many myoblasts fuse to form one
skeletal muscle fiber. Once fusion has occurred, a skeletal muscle fiber loses the ability to undergo cell division, but
satellite cells retain this ability. (b–d) The sarcolemma of the fiber encloses sarcoplasm and myofibrils, which are striated.
Sarcoplasmic reticulum wraps around each myofibril. Thousands of transverse tubules, filled with interstitial fluid, invaginate
from the sarcolemma toward the center of the muscle fiber. A triad is a transverse tubule and the two terminal cisterns of the
sarcoplasmic reticulum on either side of it. A photomicrograph of skeletal muscle tissue is shown in Table 4.9.

The contractile elements of muscle fibers, the myofibrils, contain overlapping thick and thin filaments.

The muscle ber

Myoblasts
Satellite
cell • ø 10 to 100 mic
Perimysium around
fascicle

Satellite cell • Length about 10 cm

(a) Fusion of myoblasts into
Mitochondrion
skeletal muscle fiber
Immature
muscle fiber
Endomysium • Because each skeletal muscle ber arises during
Myofibril
Nucleus
Muscle fiber
embryonic development from the fusion of a hundred or
Sarcolemma
Sarcoplasm
more small mesodermal cells called myoblasts, each
mature skeletal muscle ber has a hundred or more
(b) Organization of a fasciculus
nuclei.

Sarcoplasmic reticulum
• Once fusion has occurred, the muscle ber loses its
Sarcolemma
ability to undergo cell division.
Myofibril
Sarcoplasm
• Thus, the number of skeletal muscle bers is set before
Nucleus
you are born, and most of these cells last a lifetime.
Thick filament
Triad: Thin filament
Transverse
tubule
Terminal
cisterns
Mitochondrion

(c) Details of a muscle fiber Sarcomere

Z disc
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 332 CHAPTER 10 • MUSCULAR TISSUE

Microscopic Anatomy of a Skeletal Muscle Fiber

Figure 10.2 Microscopic organization of skeletal muscle. (a) During embryonic development, many myoblasts fuse to form one
skeletal muscle fiber. Once fusion has occurred, a skeletal muscle fiber loses the ability to undergo cell division, but
satellite cells retain this ability. (b–d) The sarcolemma of the fiber encloses sarcoplasm and myofibrils, which are striated.
Sarcoplasmic reticulum wraps around each myofibril. Thousands of transverse tubules, filled with interstitial fluid, invaginate
from the sarcolemma toward the center of the muscle fiber. A triad is a transverse tubule and the two terminal cisterns of the
sarcoplasmic reticulum on either side of it. A photomicrograph of skeletal muscle tissue is shown in Table 4.9.

The contractile elements of muscle fibers, the myofibrils, contain overlapping thick and thin filaments.

Sarcolemma, Transverse Tubules, and Sarcoplasm

Myoblasts
Satellite
cell • The plasma membrane of a muscle cell
Perimysium around
fascicle

Satellite cell • The multiple nuclei of a skeletal muscle ber are

(a) Fusion of myoblasts into
skeletal muscle fiber
Immature
muscle fiber
Mitochondrion
located just beneath the sarcolemma.
Endomysium

Myofibril
Nucleus
Muscle fiber
Transverse (T) tubules
Sarcolemma
Sarcoplasm
• Thousands of tiny invaginations of the sarcolemma.

(b) Organization of a fasciculus

• Tunnel in from the surface toward the center of each
muscle ber.
Sarcoplasmic reticulum

Sarcolemma
• Because T tubules are open to the outside of the
Myofibril
Sarcoplasm ber, they are lled with interstitial uid.

Nucleus
• Muscle action potentials travel along the
sarcolemma and through the T tubules, quickly
Thick filament
Triad: Thin filament spreading throughout the muscle ber.
Transverse
tubule
Terminal
cisterns • This arrangement ensures that an action potential
Mitochondrion
excites all parts of the muscle ber at essentially the
(c) Details of a muscle fiber Sarcomere same instant.
Z disc
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 332 CHAPTER 10 • MUSCULAR TISSUE

Microscopic Anatomy of a Skeletal Muscle Fiber

Figure 10.2 Microscopic organization of skeletal muscle. (a) During embryonic development, many myoblasts fuse to form one
skeletal muscle fiber. Once fusion has occurred, a skeletal muscle fiber loses the ability to undergo cell division, but
satellite cells retain this ability. (b–d) The sarcolemma of the fiber encloses sarcoplasm and myofibrils, which are striated.
Sarcoplasmic reticulum wraps around each myofibril. Thousands of transverse tubules, filled with interstitial fluid, invaginate
from the sarcolemma toward the center of the muscle fiber. A triad is a transverse tubule and the two terminal cisterns of the
sarcoplasmic reticulum on either side of it. A photomicrograph of skeletal muscle tissue is shown in Table 4.9.

The contractile elements of muscle fibers, the myofibrils, contain overlapping thick and thin filaments.

Myo brils
Satellite
cell
• At high magni cation, the sarcoplasm appears
Myoblasts
Perimysium around
fascicle stuffed with little threads, structures called
(a) Fusion of myoblasts into
Satellite cell
myo brils.
Mitochondrion
skeletal muscle fiber
Immature
muscle fiber
Endomysium • Myo brils are the contractile organelles of skeletal
Myofibril
Nucleus
Muscle fiber
muscle.
Sarcolemma
Sarcoplasm • ø 2 mic, and extend the entire length of a muscle
ber.
(b) Organization of a fasciculus
• Their striations make the entire skeletal muscle ber
Sarcoplasmic reticulum
appear striated.
Sarcolemma

Myofibril
Sarcoplasmic reticulum
Sarcoplasm
• A uid- lled system of membranous sacs.
Nucleus • SR encircles each myo bril.
Thick filament • This elaborate system is similar to smooth
Triad: Thin filament
Transverse
tubule
endoplasmic reticulum in non muscular cells.
Terminal
cisterns
Mitochondrion
• Dilated end sacs of the SR called terminal cisterns
butt against the T tubule from both sides.
Sarcomere
(c) Details of a muscle fiber
Z disc • A transverse tubule and the two terminal cisterns on
either side of it form a triad.
Medical Physiology I
• A triad is a T tubule and the two terminal cisterns of
the SR on either side of it.
• In a relaxed ber, the SR stores Ca2.
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10.2 SKELETAL MUSCLE TISSUE 333

Sarcoplasm
Sarcolemma Sarcoplasmic
Transverse
tubule Terminal cistern
• The cytoplasm of a muscle ber.
reticulum (SR) of SR

• Contains
Sarcoplasm • Glycogen
• in large amounts

Nucleus
• can be used for synthesis of ATP.

Z disc Thick Thin Z disc

• Myoglobin
Membrane
protein filament filament

• found only in muscle

Dystrophin
Sarcomere • binds oxygen molecules that diffuse into
muscle bers from interstitial uid
Myofibril

• myoglobin releases oxygen when it is needed

Mitochondrion Myoglobin Glycogen granules
by the mitochondria for ATP production.
• Mitochondria
• lie in rows throughout the muscle ber,
Key: strategically close to the contractile muscle
= Ca2+
= Ca2+ active
proteins that use ATP during contraction so that
transport pumps
= Ca2+ release
ATP can be produced quickly as needed.
channels

(d) Simplistic representation of a muscle fiber

Which structure shown here releases calcium ions to trigger muscle contraction?
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 Microscopic Anatomy of a Skeletal Muscle Fiber

Muscular hyperplasia Muscular hypertrophy

• Increase in the number of bers. • hyper-, above or excessive; -trophy, nourishment
• Increased production of myo brils, mitochondria,
sarcoplasmic reticulum, and other organelles.
• It results from very forceful, repetitive muscular activity, such
as strength training.
• Because hypertrophied muscles contain more myo brils, they
are capable of more forceful contractions.
• During childhood, human growth hormone and other
hormones stimulate an increase in the size of skeletal muscle
bers.
• The hormone testosterone promotes further enlargement of
muscle bers.
• A few myoblasts do persist in mature skeletal muscle as
satellite cells.
• Satellite cells retain the capacity to fuse with one another or
with damaged muscle bers to regenerate functional muscle
bers.
• However, the number of new skeletal muscle bers that can be
formed by satellite cells is not enough to compensate for
signi cant skeletal muscle damage or degeneration.
• In such cases, skeletal muscle tissue undergoes brosis, the
replacement of muscle bers by brous scar tissue.
• Thus, regeneration of skeletal muscle tissue is limited.
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 Microscopic Anatomy of a Skeletal Muscle Fiber

Muscular atrophy
• a-, without, -trophy, nourish- ment.
• It is a wasting away of muscles.
• Individual muscle bers decrease in size as a result of
progressive loss of myo brils.
• Muscular atrophy that occurs because muscles are not
used is termed disuse atrophy.
• Bedridden individuals and people with casts experience
disuse atrophy because the ow of nerve impulses
(nerve action potentials) to inactive skeletal muscle is
greatly reduced, but the condition is reversible.
• If the nerve supply to a muscle is disrupted or cut, the
muscle undergoes denervation atrophy. Over a period of
6 months to 2 years, the muscle shrinks to about one-
fourth its original size, and the muscle bers are
irreversibly replaced by brous connective tissue.
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mostly of the protein myosin. Both thin and thick fila- The I band is a lighter, less dense area that contains the rest of the
irectly involved in the contractile process. Overall, thin filaments but no thick filaments (Figure 10.3b), and a Z disc
o thin filaments for every thick filament in the regions
verlap. The filaments inside a myofibril do not extend
ngth of a muscle fiber. Instead, they are arranged in
Microscopic Anatomy of a Skeletal Muscle Fiber
passes through the center of each I band. A narrow H zone in the
center of each A band contains thick but not thin filaments. A
mnemonic that will help you to remember the composition of the I
ts called sarcomeres (SAR-kō-mērs; -mere ! part), and H bands is as follows: the letter I is thin (contains thin filaments),
e basic functional units of a myofibril (Figure 10.3a). while the letter H is thick (contains thick filaments). Supporting pro-
teins that hold the thick filaments together at the center of the H zone
er (nm) is 10#9 meter (0.001 !m); one micrometer (!m) ! form the M line, so named because it is at the middle of the sarco-
n inch. mere. Table 10.1 summarizes the components of the sarcomere.
Filaments
.3 The arrangement of filaments within a sarcomere. A sarcomere extends from one Z disc to the next.
• Within myo brils are smaller protein structures called
Myofibrils contain two types of filaments: thick filaments and thin filaments.

Thick Thin
laments or myo laments.
I band Z disc H zone A band filament filament Z disc I band
M line
• Thin laments are ø nm and 1–2 µm long, composed
mostly of the protein actin.
• Thick laments are ø 16 nm in diameter and 1–2 µm
Sarcomere
long, composed mostly of the protein myosin.
(a) Myofibril

• Both thin and thick laments are directly involved in the

Thin filament
Thick filament
Titin filament
contractile process.
Z disc M line Z disc

• Overall, there are two thin laments for every thick

lament in the regions of lament overlap.
Sarcomere

Zone of Zone of
H zone
overlap overlap
I band A band I band

(b) Details of filaments and Z discs

f the following is the smallest: muscle fiber, thick filament, or myofibril? Which is largest?

Medical Physiology I
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mostly of the protein myosin. Both thin and thick fila- The I band is a lighter, less dense area that contains the rest of the
irectly involved in the contractile process. Overall, thin filaments but no thick filaments (Figure 10.3b), and a Z disc
o thin filaments for every thick filament in the regions
verlap. The filaments inside a myofibril do not extend
ngth of a muscle fiber. Instead, they are arranged in
Microscopic Anatomy of a Skeletal Muscle Fiber
passes through the center of each I band. A narrow H zone in the
center of each A band contains thick but not thin filaments. A
mnemonic that will help you to remember the composition of the I
ts called sarcomeres (SAR-kō-mērs; -mere ! part), and H bands is as follows: the letter I is thin (contains thin filaments),
e basic functional units of a myofibril (Figure 10.3a). while the letter H is thick (contains thick filaments). Supporting pro-
teins that hold the thick filaments together at the center of the H zone
er (nm) is 10#9 meter (0.001 !m); one micrometer (!m) ! form the M line, so named because it is at the middle of the sarco-
n inch. mere. Table 10.1 summarizes the components of the sarcomere.
Sarcomere
.3 The arrangement of filaments within a sarcomere. A sarcomere extends from one Z disc to the next.
Myofibrils contain two types of filaments: thick filaments and thin filaments.
• The basic functional units of a myo bril.
Thick Thin
I band Z disc H zone A band filament filament Z disc I band • The laments inside a myo bril do not extend the entire
M line
length of a muscle ber. They are rather arranged in
compartments called sarcomeres.
• Narrow, plate-shaped regions of dense protein material
Sarcomere
called Z discs separate one sarcomere from the next.
(a) Myofibril
• Thus, a sarcomere extends from one Z disc to the next Z
Thin filament
Thick filament disc.
Titin filament
Z disc M line Z disc
• The extent of overlap of the thick and thin laments
depends on whether the muscle is contracted, relaxed, or
Sarcomere
stretched.
Zone of
overlap
H zone
Zone of
overlap • The pattern of their overlap, consisting of a variety of
I band A band I band zones and bands, creates the striations that can be seen
(b) Details of filaments and Z discs
both in single myo brils and in whole muscle bers.
f the following is the smallest: muscle fiber, thick filament, or myofibril? Which is largest?

Medical Physiology I
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mostly of the protein myosin. Both thin and thick fila- The I band is a lighter, less dense area that contains the rest of the
irectly involved in the contractile process. Overall, thin filaments but no thick filaments (Figure 10.3b), and a Z disc

Microscopic Anatomy of a Skeletal Muscle Fiber

o thin filaments for every thick filament in the regions
verlap. The filaments inside a myofibril do not extend
ngth of a muscle fiber. Instead, they are arranged in
passes through the center of each I band. A narrow H zone in the
center of each A band contains thick but not thin filaments. A
mnemonic that will help you to remember the composition of the I
ts called sarcomeres (SAR-kō-mērs; -mere ! part), and H bands is as follows: the letter I is thin (contains thin filaments),
e basic functional units of a myofibril (Figure 10.3a). while the letter H is thick (contains thick filaments). Supporting pro-
teins that hold the thick filaments together at the center of the H zone
er (nm) is 10#9 meter (0.001 !m); one micrometer (!m) ! form the M line, so named because it is at the middle of the sarco-
n inch. mere. Table 10.1 summarizes the components of the sarcomere.
Sarcomere
.3 The arrangement of filaments within a sarcomere. A sarcomere extends from one Z disc to the next.
Myofibrils contain two types of filaments: thick filaments and thin filaments.
• The darker middle part of the sarcomere is the A band,
Thick Thin
which extends the entire length of the thick laments.
I band Z disc H zone A band filament filament Z disc I band
M line
• Toward each end of the A band is a zone of overlap,
where the thick and thin laments lie side by side.
• The I band is a lighter, less dense area that contains the
Sarcomere
rest of the thin laments but no thick laments.
(a) Myofibril
• A Z disc passes through the center of each I band.
Thin filament
Thick filament

Z disc M line
Titin filament
Z disc
• A narrow H zone in the center of each A band contains
thick but not thin laments.
• Supporting proteins that hold the thick laments
Sarcomere
together at the center of the H zone form the M line, so
Zone of
overlap
H zone
Zone of
overlap named because it is at the middle of the sarcomere.
I band A band I band

(b) Details of filaments and Z discs

f the following is the smallest: muscle fiber, thick filament, or myofibril? Which is largest?

Medical Physiology I
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10.2 SKELETAL MUSCLE TISSUE 335

TABLE 10.1

Components of a Sarcomere
COMPONENT DESCRIPTION

Z discs Narrow, plate-shaped regions of dense material that separate one Z disc M line Z disc
sarcomere from the next.
A band Dark, middle part of sarcomere that extends entire length of thick
filaments and includes those parts of thin filaments that overlap
thick filaments.
I band Lighter, less dense area of sarcomere that contains remainder of
thin filaments but no thick filaments. A Z disc passes through
center of each I band.
H zone Narrow region in center of each A band that contains thick H zone
filaments but no thin filaments.
I band A band I band
M line Region in center of H zone that contains proteins that hold thick
filaments together at center of sarcomere. Sarcomere

TEM 21,600x

Exercise-Induced
CLINICAL CONNECTION |
Muscle Damage
Comparison of electron micrographs of muscle tissue taken from ath-
letes before and after intense exercise reveals considerable exercise-
induced muscle damage, including torn sarcolemmas in some muscle
is shaped like two golf clubs twisted together (Figure 10.4a). The
myosin tail (twisted golf club handles) points toward the M line in
the center of the sarcomere. Tails of neighboring myosin molecules
lie parallel to one another, forming the shaft of the thick filament.
The two projections of each myosin molecule (golf club heads) are
called myosin heads. The heads project outward from the shaft in a
 Microscopic Anatomy of a Skeletal Muscle Fiber

Myo brils Structure of thick and thin laments

• Built from three kinds of proteins Thick lament
• Contractile proteins, which generate force during • A thick lament contains about 300 myosin
contraction8/12/10
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AM Page 336 molecules, one of which is shown enlarged.
• Regulatory proteins, which help switch the • The myosin tails form the shaft of the thick
contraction process on and off lament.
• Structural proteins, which keep the thick and thin • The myosin heads project outward toward the
laments in the proper alignment, give the myo bril surrounding thin laments.
336 CHAPTER 10 • MUSCULAR TISSUE
elasticity and extensibility, and link the myo brils Thin laments
to the sarcolemma and extracellular matrix.
Figure 10.4 Structure of thick and thin filaments. (a) A thick filament• contains
Thin about
laments
300contain actin, troponin,
myosin molecules, and is shown
one of which
enlarged. The myosin tails form the shaft of the thick filament,tropomyosin.
and the myosin heads project outward toward the
surrounding thin filaments. (b) Thin filaments contain actin,• troponin, and tropomyosin.
Contractile proteins (myosin and actin) generate
force during
Contractile proteins (myosin and actin) generate force during contraction; contraction.
regulatory proteins (troponin and tropomyosin)
help switch contraction on and off. • Regulatory proteins (troponin and tropomyosin)
Thick filament help switch contraction on and off.
Actin Troponin Tropomyosin

Myosin tail Myosin heads

Myosin-binding site (covered by tropomyosin)

(a) A thick filament and a myosin molecule (b) Portion of a thin filament

Which proteins connect into the Z disc? Which proteins are present in the A band? In the I band?
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 Microscopic Anatomy of a Skeletal Muscle Fiber

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Myosin
• Myosin is the main component of thick laments
• Functions as a motor protein in all three types of muscle tissue.
• Motor proteins pull various cellular structures to achieve movement by converting the chemical energy in ATP to
336 CHAPTER 10 • MUSCULAR TISSUE
the mechanical energy of motion. JWCL316_c10_327-365.qxd 8/12/10 6:15 AM Page 334

• In skeletal muscle, about 300 molecules of myosin form a single thick lament. 334 CHAPTER 10 • MUSCULAR TISSUE

both sides. A transverse tubule and the two terminal cisterns on Narrow, plate-shaped regions of dense protein ma

• Each myosin molecule is shaped like two golf clubs twisted together. either side of it form a triad (tri- ! three). In a relaxed muscle
fiber, the sarcoplasmic reticulum stores calcium ions (Ca2"). Re-
Z discs separate one sarcomere from the next. Thus
extends from one Z disc to the next Z disc.

• The myosin tailFigure 10.4clubStructure of thick and

thethin filaments.
lease of Ca2" from the terminal cisterns of the sarcoplasmic retic-

(a)ofAthe
thick filament contains about 30
The extent of overlap of the thick and thin filamen
ulum triggers muscle contraction. whether the muscle is contracted, relaxed, or stretched
of their overlap, consisting of a variety of zones and
(twisted golf handles) points toward M line in the center sarcomere.
Filaments and the Sarcomere ure 10.3b), creates the striations that can be seen both

enlarged. The myosin tails form the shaft of the thick filament, and the myosin
Within myofibrils are smaller protein structures called filaments ofibrils and in whole muscle fibers. The darker midd
or myofilaments (Figure 10.2c). Thin filaments are 8 nm in diam- sarcomere is the A band, which extends the entire
eter and 1–2 !m long† and composed mostly of the protein actin, thick filaments (Figure 10.3b). Toward each end of th

• Tails of neighboring myosin molecules lie parallel to one another, forming the shaft of the thick lament.
while thick filaments are 16 nm in diameter and 1–2 !m long and zone of overlap, where the thick and thin filaments lie

surrounding thin filaments. (b) Thin filaments contain actin, troponin, and tropo
composed mostly of the protein myosin. Both thin and thick fila- The I band is a lighter, less dense area that contains t
ments are directly involved in the contractile process. Overall, thin filaments but no thick filaments (Figure 10.3b),
there are two thin filaments for every thick filament in the regions passes through the center of each I band. A narrow H

• The two projections of each myosin molecule (golf club heads) are called myosin heads.
of filament overlap. The filaments inside a myofibril do not extend
the entire length of a muscle fiber. Instead, they are arranged in
compartments called sarcomeres (SAR-kō-mērs; -mere ! part),
center of each A band contains thick but not thin
mnemonic that will help you to remember the compo
and H bands is as follows: the letter I is thin (contains th
which are the basic functional units of a myofibril (Figure 10.3a). while the letter H is thick (contains thick filaments). Su

Contractile
• The heads project outward from proteins
the shaft in (myosin
a spiraling and
fashion, actin)
each generate
extending towardforce
†
during
one of the sixcontraction;
thin lamentsregul
One nanometer (nm) is 10#9 meter (0.001 !m); one micrometer (!m) !
1/25,000 of an inch.
teins that hold the thick filaments together at the center
form the M line, so named because it is at the middle
mere. Table 10.1 summarizes the components of the s

help switch contraction on and off.

that surround each thick lament. Figure 10.3 The arrangement of filaments within a sarcomere. A sarcomere extends from one Z disc to the next.
Myofibrils contain two types of filaments: thick filaments and thin filaments.

Thick Thin
I band Z disc H zone A band filament filament Z disc I band

Thick filament
M line

Actin Tro
Sarcomere

(a) Myofibril

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

Myosin tail Myosin heads Sarcomere

Zone of Zone of
H zone
overlap overlap
I band A band I band

(b) Details of filaments and Z discs

Which of the following is the smallest: muscle fiber, thick filament, or myofibril? Which is largest?
Myos

(a) A thick filament and a myosin molecule

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 Microscopic Anatomy of a Skeletal Muscle Fiber

Actin
• Thin
Page 336 laments are anchored to Z discs.
• The main component of the thin laments is the protein actin.
• Individual actin molecules join to form an actin lament that is twisted into a helix. JWCL316_c10_327-365.qxd 8/12/10 6:15 AM Page 334

• On each actin molecule is a myosin-binding site, where a myosin head can attach. 334 CHAPTER 10 • MUSCULAR TISSUE

both sides. A transverse tubule and the two terminal cisterns on Narrow, plate-shaped regions of dense protein ma

SUE • Smaller amounts of two regulatory proteins -tropomyosin and troponin- are also part of the thin lament.
either side of it form a triad (tri- ! three). In a relaxed muscle
fiber, the sarcoplasmic reticulum stores calcium ions (Ca2"). Re-
lease of Ca2" from the terminal cisterns of the sarcoplasmic retic-
ulum triggers muscle contraction.
Filaments and the Sarcomere
Z discs separate one sarcomere from the next. Thus
extends from one Z disc to the next Z disc.
The extent of overlap of the thick and thin filamen
whether the muscle is contracted, relaxed, or stretched
of their overlap, consisting of a variety of zones and
ure 10.3b), creates the striations that can be seen both

• In relaxed muscle, myosin is blocked from binding to actin because strands of tropomyosin cover the myosin-
Within myofibrils are smaller protein structures called filaments
or myofilaments (Figure 10.2c). Thin filaments are 8 nm in diam-
eter and 1–2 !m long† and composed mostly of the protein actin,
ofibrils and in whole muscle fibers. The darker midd
sarcomere is the A band, which extends the entire
thick filaments (Figure 10.3b). Toward each end of th

hin filaments.
binding (a) A on
sites thick filament contains about 300 myosin molecules, one of which is shown
actin.
while thick filaments are 16 nm in diameter and 1–2 !m long and
composed mostly of the protein myosin. Both thin and thick fila-
ments are directly involved in the contractile process. Overall,
zone of overlap, where the thick and thin filaments lie
The I band is a lighter, less dense area that contains t
thin filaments but no thick filaments (Figure 10.3b),

s form the shaft of the thick filament, and the myosin heads project outward toward the
there are two thin filaments for every thick filament in the regions passes through the center of each I band. A narrow H
of filament overlap. The filaments inside a myofibril do not extend center of each A band contains thick but not thin
the entire length of a muscle fiber. Instead, they are arranged in mnemonic that will help you to remember the compo

s. (b) •Thin
Thefilaments
tropomyosin strands
actin,introponin,
turn are and
heldtropomyosin.
in place by troponin molecules. compartments called sarcomeres (SAR-kō-mērs; -mere ! part), and H bands is as follows: the letter I is thin (contains th

contain which are the basic functional units of a myofibril (Figure 10.3a).

†
One nanometer (nm) is 10#9 meter (0.001 !m); one micrometer (!m) !
while the letter H is thick (contains thick filaments). Su
teins that hold the thick filaments together at the center
form the M line, so named because it is at the middle
1/25,000 of an inch. mere. Table 10.1 summarizes the components of the s

• When Ca2 binds to troponin → → → troponin undergoes a change in shape → → → moves tropomyosin
and actin) generate force during contraction; regulatory proteins (troponin and tropomyosin) Figure 10.3 The arrangement of filaments within a sarcomere. A sarcomere extends from one Z disc to the next.
Myofibrils contain two types of filaments: thick filaments and thin filaments.

nd off. away from myosin-binding sites on actin → → → myosin binds to actin → → → muscle contraction begins I band Z disc H zone
M line
A band
Thick
filament
Thin
filament Z disc I band

Sarcomere

Actin Troponin Tropomyosin (a) Myofibril

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

Myosin heads Sarcomere

Zone of Zone of
H zone
overlap overlap
I band A band I band

(b) Details of filaments and Z discs

Myosin-binding site (covered by tropomyosin)

Which of the following is the smallest: muscle fiber, thick filament, or myofibril? Which is largest?

n molecule (b) Portion of a thin filament

isc? Which proteins are present in the A band? In the I band?

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 Microscopic Anatomy of a Skeletal Muscle Fiber
JWCL316_c10_327-365.qxd 8/12/10 6:15 AM Page 333

10.2 SKELETAL MUSCLE TISSUE 333

Sarcolemma Sarcoplasmic
reticulum (SR)
Transverse
tubule Terminal cistern
of SR
Dystrophin

Sarcoplasm
Function
• Dystrophin is a protein located between the
Nucleus
sarcolemma and the outermost layer of
Membrane
protein
Z disc Thick
filament
Thin
filament
Z disc
myo laments in the muscle ber (myo ber).
Dystrophin
Sarcomere
• It links thin laments of the sarcomere to integral
Myofibril
membrane proteins of the sarcolemma, which are
attached in turn to proteins in the connective
Mitochondrion Myoglobin Glycogen granules
tissue extracellular matrix that surrounds muscle
bers.
Key:

= Ca2+ • Dystrophin and its associated proteins are thought

= Ca2+ active
transport pumps
= Ca2+ release
channels
to reinforce the sarcolemma and help transmit the
(d) Simplistic representation of a muscle fiber

Which structure shown here releases calcium ions to trigger muscle contraction?
tension generated by the sarcomeres to the
tendons.
• It is a cohesive protein, linking actin laments to
other support proteins that reside on the inside
surface of each muscle ber's plasma membrane
(sarcolemma).
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 Microscopic Anatomy of a Skeletal Muscle Fiber

Dystrophin
Pathology
• Dystrophin de ciency has been de nitively
established as one of the root causes of the general
class of myopathies collectively referred to as
muscular dystrophy.
• Normal skeletal muscle tissue contains only small
amounts of dystrophin (about 0.002% of total muscle
protein).
• But its absence (or abnormal expression) leads to the
development of a severe and currently incurable
constellation of symptoms most readily characterized
by several aberrant intracellular signaling pathways
that ultimately yield pronounced myo ber necrosis as
well as progressive muscle weakness and fatigability.
• The deletions of one or several exons of the
dystrophin DMD gene cause Duchenne and Becker
muscular dystrophies.
• Most DMD patients become wheelchair-dependent
early in life, and the gradual development of cardiac
hypertrophy—a result of severe myocardial brosis
—typically results in premature death in the rst two
or three decades of life.
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 Microscopic Anatomy of a Skeletal Muscle Fiber
Titin
Structure
• Titin also contains binding sites for muscle-
associated proteins so it serves as an adhesion
template for the assembly of contractile machinery in
muscle cells.
• It comprises 244 individually folded protein domains
connected by unstructured peptide sequences.
• These domains unfold when the protein is stretched
and refold when the tension is removed.
• Titin is important in the contraction of striated
muscle tissues.
• It connects the Z disc to the M line in the sarcomere.
• Titin (also called connectin).
• The name titin is derived from the Greek Titan (a
giant deity, anything of great size).
• Titin is the third most abundant protein in muscle
(after myosin and actin), and an adult human contains
approximately 0.5 kg of titin.
• With its length of ~27,000 to ~35,000 amino acids
(depending on the splice isoform), titin is the largest
known protein.
• Huge size. MW 3 million daltons, 50 times larger
than an average-sized protein.
• Titin is a giant protein, greater than 1 µm in length
that functions as a molecular spring that is
responsible for the passive elasticity of muscle.
• An N-terminal Z-disc region and a C-terminal M-line
region bind to the Z-line and M-line of the
sarcomere, respectively, so that a single titin
molecule spans half the length of a sarcomere.
• Each titin molecule spans half a sarcomere, from a Z
disc to an M line, a distance of 1 to 1.2 mic in relaxed
muscle.
•
Microscopic Anatomy of a Skeletal Muscle Fiber

Titin
Function
• To stabilize the thick lament.
• To center it between the thin laments.
• To recoil the sarcomere like a spring after it is
stretched.
• The protein contributes to force transmission at
the Z disc and resting tension in the I band
region.
• It limits the range of motion of the sarcomere in
tension, thus contributing to the passive
stiffness of muscle.
• The part of the titin molecule that extends from
the Z disc is very elastic. It accounts for much
of the elasticity and extensibility of myo brils.
• Variations in the sequence of titin between
different types of striated muscle (cardiac or
skeletal) have been correlated with differences
in the mechanical properties of these muscles.
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Microscopic Anatomy of a Skeletal Muscle Fiber

Titin
Clinical relevance
• Titin mutations are associated with
• Hereditary myopathy with early respiratory failure.
• Early-onset myopathy with fatal cardiomyopathy
• Core myopathy with heart disease
• Centronuclear myopathy
• Limb-girdle muscular dystrophy type 2J
• Familial dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Tibial muscular dystrophy.
• Genetically linked form of any dystrophy or
myopathy
• Dilated cardiomyopathy
• Autoantibodies to titin are produced in patients with the
autoimmune disease Myasthenia gravis.
 Microscopic Anatomy of a Skeletal Muscle Fiber

Myomesin
• Forms the M line.
• The M line proteins bind to titin and connect
adjacent thick laments to one another.
• Myosin holds the thick laments in alignment at the
M line.
Nebulin
• It is a long, nonelastic protein wrapped around the
entire length of each thin lament.
• It helps anchor the thin laments to the Z discs and
regulates the length of thin laments during
development.
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helping stabilize the position of the thick filament. The part of the
titin molecule that extends from the Z disc is very elastic. Because it
can stretch to at least four times its resting length and then spring
back unharmed, titin accounts for much of the elasticity and exten-
sibility of myofibrils. Titin probably helps the sarcomere return to its
resting length after a muscle has contracted or been stretched, may
Muscle contraction
help prevent overextension of sarcomeres, and maintains the central
location of the A bands.
The dense material of the Z discs contains molecules of
!-actinin, which bind to actin molecules of the thin filament and
to titin. Molecules of the protein myomesin (mı̄-ō-MĒ-sin) form
the M line. The M line proteins bind to titin and connect adjacent
thick filaments to one another. Myosin holds the thick filaments in
alignment at the M line. Nebulin (NEB-ū-lin) is a long, nonelas-
tic protein wrapped around the entire length of each thin filament.
It helps anchor the thin filaments to the Z discs and regulates the

TABLE 10.2 Muscle Proteins

Summary of Skeletal Muscle Fiber Proteins
TYPE OF PROTEIN DESCRIPTION

Contractile proteins Proteins that generate force during muscle contractions.

Myosin Contractile protein that makes up thick filament; molecule consists of a tail and two myosin heads, which bind to myosin-
binding sites on actin molecules of thin filament during muscle contraction.
Actin Contractile protein that is the main component of thin filament; each actin molecule has a myosin-binding site where myosin
head of thick filament binds during muscle contraction.
Regulatory proteins Proteins that help switch muscle contraction process on and off.
Tropomyosin Regulatory protein that is a component of thin filament; when skeletal muscle fiber is relaxed, tropomyosin covers
myosin-binding sites on actin molecules, thereby preventing myosin from binding to actin.
Troponin Regulatory protein that is a component of thin filament; when calcium ions (Ca2!) bind to troponin, it changes shape; this
conformational change moves tropomyosin away from myosin-binding sites on actin molecules, and muscle contraction
subsequently begins as myosin binds to actin.
Structural proteins Proteins that keep thick and thin filaments of myofibrils in proper alignment, give myofibrils elasticity and extensibility, and link
myofibrils to sarcolemma and extracellular matrix.
Titin Structural protein that connects Z disc to M line of sarcomere, thereby helping to stabilize thick filament position; can stretch
and then spring back unharmed, and thus accounts for much of the elasticity and extensibility of myofibrils.
!-Actinin Structural protein of Z discs that attaches to actin molecules of thin filaments and to titin molecules.
Myomesin Structural protein that forms M line of sarcomere; binds to titin molecules and connects adjacent thick filaments to one another.
Nebulin Structural protein that wraps around entire length of each thin filament; helps anchor thin filaments to Z discs and regulates
length of thin filaments during development.
Dystrophin Structural protein that links thin filaments of sarcomere to integral membrane proteins in sarcolemma, which are attached in turn
to proteins in connective tissue matrix that surrounds muscle fibers; is thought to help reinforce sarcolemma and help transmit
tension generated by sarcomeres to tendons.
Medical Physiology I