MUSCLE TISSUE cells remains adjacent to most fibers of

differentiated skeletal muscle.

 Actin microfilaments and associated
proteins generate the forces necessary for (a) Skeletal muscle is composed of large,
the muscle contraction. elongated, multinucleated fibers that show
strong, quick, voluntary contractions.
 muscle cells are of mesodermal origin
(b) Cardiac muscle is composed of irregular
 differentiate by a gradual process of cell branched cells bound together longitudinally
lengthening by intercalated discs and shows strong,
involuntary contractions.
 abundant synthesis of the myofibrillar
proteins actin and myosin. (c) Smooth muscle is composed of grouped,
fusiform cells with weak, involuntary
 Skeletal muscle contains bundles of very
contractions.
long, multinucleated cells with cross-
striations.  Thin layers of connective tissue surround
and organize the contractile fibers in all
 contraction is quick, forceful
three types of muscle,
 under voluntary control.
 epimysium, an external sheath of dense
 Cardiac muscle: cross-striations and is irregular connective tissue, surrounds the
composed of elongated, often branched entire muscle
cells bound to one another at structures
 perimysium is a thin connective tissue
called intercalated discs
layer that immediately surrounds each
 unique to cardiac muscle. bundle of muscle fibers termed a fascicle

 Contraction is involuntary,  Each fascicle of muscle fibers makes up a

vigorous, and rhythmic functional unit in which the fibers work
together.
 Smooth muscle: consists of collections of
fusiform cells which lack striations and  delicate layer of reticular fibers
have slow, involuntary contractions. and scattered fibroblasts

 muscle cell membrane and its external  endomysium, surrounds the external
lamina are the sarcolemma lamina of individual muscle fibers.

 Skeletal (or striated) muscle consists of  capillaries form a rich network in

muscle fibers: long, cylindrical the endomysium bringing O2 to
multinucleated cells with diameters of 10- the muscle
100 μm.
 myotendinous junctions which join the
 Embryonic muscle development: muscle to bone, skin, or another muscle.
mesenchymal myoblasts fuse, forming
 collagen fibers from the tendon
myotubes with many nuclei. Myotubes
insert themselves among muscle
then further differentiate to form striated
fibers and associate directly with
muscle fibers
complex infoldings of sarcolemma.
 A small population of reserve progenitor
Organization Within Muscle Fibers
cells called muscle satellite
 Longitudinally sectioned skeletal muscle  proliferate and produce new muscle
fibers: alternating light and dark bands fibers following muscle injury
 Sarcoplasm: highly organized, containing  I bands: is seen to be bisected by a dark
primarily long cylindrical filament bundles transverse line, the Z disc
called myofibrils
 Sarcomere: The repetitive functional
 dark bands on the myofibrils are called A subunit of the contractile apparatus
bands (anisotropic or birefringent in
polarized light microscopy)  extends from Z disc to Z disc

 light bands are called I bands (isotropic, do  lateral registration of sarcomeres in

not alter polarized light). adjacent myofibrils causes the entire
muscle fiber to exhibit a characteristic
pattern of transverse striations
 Myofibrils consist of an end-to-end
repetitive arrangement of sarcomeres.
 The A and I banding pattern in sarcomeres
is due mainly to the regular arrangement
of thick and thin myofilaments, composed
of myosin and F-actin,
 thick myosin filaments: occupy the A band
at the middle region of the sarcomere.
 Myosin: is a large complex with two
identical heavy chains and two pairs
of light chains.
 Myosin heavy chains are thin, rodlike
 Skeletal muscle begins to differentiate motor proteins twisted together as myosin
when mesenchymal cells, called tails
myoblasts, align and fuse together to
make longer, multinucleated tubes called  four myosin light chains form a head at one
myotubes. end of each heavy chain.

 Myotubes synthesize the proteins to make  The myosin heads bind both actin, forming
up myofilaments and gradually begin to transient crossbridges between the thick
show cross-striations by light microscopy. and thin filaments, and ATP, catalyzing
energy release (actomyosin ATPase
 satellite cells: Part of the myoblast activity)
population
 Each G-actin monomer contains a binding
 does not fuse and differentiate but site for myosin
remains as a group of mesenchymal
cells.  two tightly associated regulatory proteins
in thin filaments
 located on the external surface of
muscle fibers inside the developing
external lamina.
 Tropomyosin: two polypeptide chains corresponds to a region with only the rodlike
located in the groove between the two portions of the myosin molecule and no thin
twisted actin strands filaments.
 Troponin: a complex of three subunits: M line: Seen when H zone is bisected.
 TnT: attaches to tropomyosin 1. myomesin
 TnC: binds Ca2 2. creatine kinase.
 TnI: regulates the actin-myosin Myomesin: a myosin-binding protein that
interaction holds the thick filaments in place
 Troponin complexes: attach at specific sites creatine kinase: An enzyme that catalyzes
regularly spaced along each tropomyosin transfer of phosphate groups from
molecule. phosphocreatine (a storage form of high-
energy phosphate groups) to ADP
myosin and actin: represent over half of the
I bands: consist of the portions of the thin total protein in striated muscle.
filaments
The overlapping arrangement of thin and
do not overlap the thick filaments in the
thick filaments within sarcomeres produces in
A bands (I bands stain more lightly than A TEM cross sections hexagonal patterns
bands)
Actin filaments are anchored perpendicularly
on the Z disc by the actin-binding protein α- Sarcoplasmic Reticulum & Transverse Tubule
actinin System
exhibit opposite polarity on each side of this
disc
membranous smooth ER: sarcoplasmic
Titin: accessory protein in I bands reticulum
largest protein in the body with scaffolding  contains pumps and other proteins for
and elastic properties Ca2+ sequestration and surrounds the
myofibrils
supports the thick myofilaments and connects
them to the Z disc Calcium release from cisternae of the
sarcoplasmic reticulum through voltage-gated
Nebulin: binds each thin myofilament laterally Ca2+ channels is triggered by membrane
helps anchor them to α-actinin depolarization produced by a motor nerve.

specifies the length of the actin polymers the sarcolemma has tubular infoldings called
during myogenesis transverse or T-tubules

A bands: contain both the thick filaments and  long fingerlike invaginations of the cell
the overlapping portions of thin filaments. membrane

H zone: lighter zone that is present in its  penetrate deeply into the sarcoplasm
center and encircle each myofibril near the
 aligned A- and I-band boundaries of
sarcomeres
Adjacent to each T-tubule are expanded
terminal cisternae of sarcoplasmic reticulum.
Triad: T-tubule with two terminal cisternae
allows depolarization of the sarcolemma in a T-
tubule to affect the sarcoplasmic reticulum and
trigger release of Ca2+ ions into cytoplasm
around the thick and thin filaments.
Mechanism of Contraction
neither the thick nor the thin filaments change
their length.
Contraction occurs as the overlapping thin and
thick filaments of each sarcomere slide past
one another.
The sarcolemma has deep invaginations called
Contraction is induced when an action T-tubules
potential arrives at a synapse, the
neuromuscular junction (NMJ), and is each of becomes associated with two terminal
cisternae of the sarcoplasmic reticulum.
transmitted along the T-tubules to terminal
cisternae of the sarcoplasmic reticulum to A T-tubule and its two associated terminal
trigger Ca2+ release cisterna comprise a “triad” of small spaces
along the surface of the myofibrils
resting muscle: the myosin heads cannot bind
actin because the binding sites are blocked by
the troponin-tropomyosin complex on the F-
actin filaments
Calcium ions released upon neural stimulation
bind troponin, changing its shape and moving
tropomyosin on the F-actin to expose the
myosin-binding active sites and allow
crossbridges to form
Binding actin produces a conformational
change or pivot in the myosins
When the neural impulse stops and levels of
pulls the thin filaments farther into the A band, free Ca2+ ions diminish, tropomyosin again
toward the Z disc covers the myosin-binding sites on actin and
the filaments passively slide back and
Energy for the myosin head pivot that pulls sarcomeres return to their relaxed length
actin is provided by hydrolysis of ATP bound to
the myosin heads. absence of ATP: the actin-myosin crossbridges
become stable
rigidity of skeletal muscles (rigor mortis) that diffuses across the cleft, and binds to its
occurs as mitochondrial activity stops after receptors in the folded sarcolemma.
death.
acetylcholine receptor contains a nonselective
Innervation cation channel that opens upon
neurotransmitter binding
 allowing influx of cations, depolarizing
Myelinated motor nerves branch out within the the sarcolemma, and producing the
perimysium muscle action potential.
Acetylcholinesterase:prevents prolonged
each nerve gives rise to several unmyelinated contact of the transmitter with its receptors
terminal twigs that pass through endomysium muscle action potential moves along the
and form synapses with individual muscle sarcolemma and along T-tubules which
fibers. penetrate deeply into sarcoplasm.
At triads the depolarization signal triggers the
Schwann cells: enclose the small axon release of Ca2+ from terminal cisterns of the
branches and cover their points of contact with sarcoplasmic reticulum, initiating the
the muscle cells contraction cycle.
An axon from a single motor neuron can form
MEPs with one or many muscle fibers.
Each axonal branch forms a dilated termination
situated within a trough on the muscle cell motor unit: the single axon and all the muscle
surface fibers in contact with its branches

part of the synapses termed the neuromuscular Individual striated muscle fibers do not show
junctions, or motor end plates (MEPs) graded contraction—they contract either all
the way or not at all.

all synapses the axon terminal contains

mitochondria and numerous synaptic vesicles; the fibers within a muscle fascicle do not all
here the vesicles contain the neurotransmitter contract at the same time.
acetylcholine. Myasthenia gravis: an autoimmune disorder
synaptic cleft: Between the axon and the that involves circulating antibodies against
proteins of acetylcholine receptors.
Muscle
Antibody binding to the antigenic sites
junctional folds: provide for greater interferes with acetylcholine activation of their
postsynaptic surface area and more receptors
transmembrane acetylcholine receptors
leads to intermittent periods of skeletal muscle
weakness.
When a nerve action potential reaches the The extraocular muscles of the eyes are
MEP, acetylcholine is liberated from the axon commonly the first affected.
terminal
1 A nerve impulse triggers release of ACh from interstitial fluid and a few thin muscle fibers
the synaptic knob into the synaptic cleft. ACh filled with nuclei and called intrafusal fibers
binds to ACh receptors in the motor end plate
of the neuromuscular junction, initiating a
muscle impulse in the sarcolemma of the Changes in length (distension) of the
muscle fiber. surrounding (extrafusal) muscle fibers caused
2. As the muscle impulse spreads quickly from by body movements are detected by the
the sarcolemma along T tubules, calcium ions muscle spindles and the sensory nerves relay
are released from terminal cisternae into the this information to the spinal cord.
sarcoplasm. Golgi tendon organs: smaller encapsulated
3. Calcium ions bind to troponin. Troponin structures that enclose sensory axons
changes shape, moving tropomyosin on the penetrating among the collagen bundles at the
actin to expose active sites on actin molecules myotendinous junction
of thin filaments. Myosin heads of thick  Tendon organs detect changes in
filaments attach to exposed active sites to form tension within tendons produced by
crossbridges. muscle contraction and act to inhibit
4. Myosin heads pivot, moving thin filaments motor nerve activity if tension
toward the sarcomere center. ATP binds becomes excessive
myosin heads and is broken down into ADP and
P. Myosin heads detach from thin filaments
and return to their prepivot position. The
repeating cycle of attach-pivot-detach-return
slides thick and thin filaments past one
another. The sarcomere shortens and the
muscle contracts. The cycle continues as long
as calcium ions remain bound to troponin to
keep active sites exposed.

Muscle Spindles & Tendon Organs

Striated muscles and myotendinous junctions
contain sensory receptors acting as
proprioceptors Dystrophin is a large actin-binding protein
 Provides the central nervous system located just inside the sarcolemma of skeletal
(CNS) with data from the muscle fibers, involved in the functional
musculoskeletal system organization of myofibrils.

Among the muscle fascicles are stretch Duchenne muscular dystrophy: mutations of
detectors known as muscle spindles the dystrophin gene can lead to defective
linkages between the cytoskeleton and the
encapsulated by modified perimysium, with extracellular matrix (ECM).
concentric layers of flattened cells, containing
Muscle contractions can disrupt these weak term contraction
linkages, causing the atrophy of muscle fibers
few mitochondria or capillaries and depending
largely on anaerobic metabolism of glucose
derived from stored glycogen, features which
Skeletal Muscle Fiber Types make such fibers appear white. Rapid
Skeletal muscles such as those that move the contractions lead to rapid fatigue as lactic acid
eyes and eyelids need to contract rapidly, while produced by glycolysis accumulates.
others such as those for bodily posture must Fast oxidative-glycolytic
maintain tension for longer periods while
resisting fatigue fibers have physiological and histological
features intermediate between those of the
Different types of fibers can be identified on other two types.
the basis of
CARDIAC MUSCLE
(1) their maximal rate of contraction (fast or
slow fibers) During embryonic development mesenchymal
cells around the primitive heart tube align into
(2) their major pathway for ATP synthesis chainlike arrays. Rather than fusing into
(oxidative phosphorylation or glycolysis). multinucleated cells/fibers as in developing
Fast versus slow rates of fiber contraction are skeletal muscle fibers
due largely to myosin isoforms with different cardiac muscle cells form complex junctions
maximal rates of ATP hydrolysis. between interdigitating processes
Myoglobin: a globular sarcoplasmic protein the heart consists of tightly knit bundles of
similar to hemoglobin which contains iron cells, interwoven in spiraling layers that provide
atoms and allows for O2 storage. for a characteristic wave of contraction that
resembles wringing out of the heart ventricles

Fiber Diversity Is Divided Into Three Major each cardiac muscle cell usually has only one
nucleus and is centrally located.
Types:
Surrounding the muscle cells is a delicate
Slow oxidative sheath of endomysium with a rich capillary
network.
muscle fibers are adapted for slow contractions
over long periods without fatigue A thicker perimysium separates bundles and
layers of muscle fibers and in specific areas
 many mitochondria
forms larger masses of fibrous connective
many surrounding capillaries tissue comprising the “cardiac skeleton.”

much myoglobin intercalated discs: A unique characteristic of

cardiac muscle is the presence of transverse
all features that make fresh tissue rich in lines that cross the fibers at irregular intervals
these fibers dark or red in color. where the myocardial cells join.

Fast glycolytic
fibers are specialized for rapid, short
 intercalated discs: represent the interfaces
between adjacent cells and consist of many
junctional complexes
Transverse regions of these irregular, steplike
discs are composed of many desmosomes and
fascia adherens junctions,
provide strong intercellular adhesion during
the cells’ constant contractile activity
The less abundant, longitudinally oriented
regions of each intercalated disc run parallel to
the myofibrils and are filled with gap junctions
Cardiac muscle fiber contraction is intrinsic and
provide ionic continuity between the cells. spontaneous.

These regions serve as “electrical synapses” Secretory granules about 0.2-0.3 μm in

promoting rapid impulse conduction through diameter are found near atrial muscle nuclei
many cardiac muscle cells simultaneously and associated with small Golgi complexes
contraction of many adjacent cells as a unit.
These granules release the peptide hormone
Mitochondria occupy up to 40% of the cell atrial natriuretic factor (ANF)
volume, higher than in slow oxidative skeletal
acts on target cells in the kidney to affect Na+
muscle fibers.
excretion and water balance.
Fatty acids: major fuel of the heart, are stored
The contractile cells of the heart’s atria thus
as triglycerides in small lipid droplets.
also serve an endocrine function.
ventricular muscle tubules: T-tubules are well-
Ischemia
developed with large lumens and penetrate the
sarcoplasm in the vicinity of the myofibrils’ Z The most common injury sustained by cardiac
discs. muscle
atrial muscle : T-tubules are much smaller or tissue damage due to lack of oxygen when
entirely absent. coronary arteries are occluded by heart
disease. Lacking muscle satellite cells
Sarcoplasmic reticulum is less well-organized in
cardiac compared to skeletal muscle fibers. adult mammalian cardiac muscle has little
potential to regenerate after injury
The junctions between its terminal cisterns and
T-tubules typically involve only one structure of
each type, forming profiles called dyads rather
than triads. SMOOTH MUSCLE
a major component of blood vessels and of the
digestive, respiratory, urinary, and
reproductive tracts and their associated organs.
also called visceral muscle
elongated, tapering, and unstriated cells, each
of which is enclosed by an external lamina
network of type I and type III collagen fibers composed of desmin attach to the dense
bodies.
The submembranous dense bodies include
At each cell’s central, broadest part, where is a cadherins of desmosomes linking adjacent
single elongated nucleus. smooth muscle cells.
close packing is achieved with the narrow ends
of each cell adjacent to the broad parts of
neighboring cells Dense bodies in smooth muscle cells thus
serve as points for transmitting the contractile
All cells are linked by numerous gap junctions. force not only within the cells, but also
Concentrated near the nucleus are between adjacent cells
mitochondria, polyribosomes, RER, and vesicles Axons of autonomic nerves passing through
of a Golgi apparatus. smooth muscle have periodic swellings or
At the smooth muscle cell surface are varicosities that lie in close contact with muscle
numerous small plasmalemma invaginations fibers.
resembling caveolae, Synaptic vesicles in the varicosities release a
compartmentalize various signaling neurotransmitter, usually acetylcholine or
components norepinephrine, which diffuses and binds
receptors in the sarcolemmae of numerous
The fibers have rudimentary sarcoplasmic muscle cells.
reticulum, but lack T-tubules
Caveolae of smooth muscle cells contain the
major ion channels that control Ca2+ There is little or no specialized structure to such
junctions
release from sarcoplasmic cisternae at
myofibrils that initiates contraction.
bundles of thin and thick myofilaments supplement fibroblast activity, synthesizing
crisscross the sarcoplasm obliquely. collagen, elastin, and proteoglycans, with a
major influence on the ECM
The myosin filaments have a less regular
arrangement among the thin filaments and Leiomyomas: Benign tumors commonly
fewer crossbridges. develop from smooth muscle fibers seldom
problematic.
smooth muscle actin filaments are not
associated with troponin and tropomyosin, most frequently occur in the wall of the
using instead calmodulin and Ca2+-sensitive uterus( fibroids)

myosin light-chain kinase (MLCK) to produce can become sufficiently large to produce
contraction. painful pressure and unexpected bleeding.

actin myofilaments insert into anchoring

cytoplasmic and plasmalemma associated › REGENERATION OF MUSCLE TISSUE
dense bodies which contain α-actinin
In skeletal muscle, although the multinucleated
Smooth muscle cells also have an elaborate cells cannot undergo mitosis, the tissue can still
array of 10-nm intermediate filaments, display limited regeneration.
 The source of regenerating cells is the sparse
population of mesenchymal satellite cells lying
inside the external lamina of each muscle fiber.
Satellite cells are inactive, reserve myoblasts
which persist after muscle differentiation.
After injury the normally quiescent satellite
cells become activated, proliferating, and
fusing to form new skeletal muscle fibers.

Cardiac muscle lacks satellite cells and shows

very little regenerative capacity beyond early
childhood. Defects or damage (eg, infarcts) to
heart muscle are generally replaced by
proliferating fibroblasts and growth of
connective tissue, forming only myocardial
scars.
Smooth muscle: composed of simpler, smaller,
mononucleated cells, is capable of a more
active regenerative response.
After injury, viable smooth muscle cells
undergo mitosis and replace the damaged
tissue