1
THE MUSCLE TISSUE
Ahmad Aulia Jusuf, MD, PhD
Depart of Histology
Faculty of Medicine University of Indonesia
involuntary cardiac muscle limited almost
INTRODUCTION
exclusively to the heart. The skeletal muscle
Muscle (Fig-1) is one of the four basic
tissue
characterized
by
its
specific
properties, the ability to convert chemical
energy
into
mechanical
work
(Fig-3) is associated with the bony skeleton
and consists of cylindrical fibers that are
multinucleated.
and
contractility that permit the locomotion,
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constriction, pumping and other propulsive
restriction
movement of the muscle to be occured.
Fig-3 Skeletal Muscle
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The cardiac muscle (Fig-4) consists of
restriction
separate cellular units and is uninucleate.
Fig-1 The muscle
Furthermore cardiac muscle is characterized
There are two major type of muscle
according to the present of repeating dark
by
rhythmic,
involuntary
contractions
controlled by autonomic innervation.
and light cross-bands or striation (Fig-2); the
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restriction
restriction
Fig-4 Cardiac Muscle
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restriction
The smooth muscle (Fig-5) consists of
spindle-shape, fusiform, uninucleate cell that
Fig-2 The striated and smooth muscles
striated muscle and and smooth muscle. The
striated muscle cells display characteristic
do not exhibit striations. Smooth muscle is
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restriction
alternation of light and dark cross-bands.
There are two types of striated muscle;
skeletal
muscle
accounting
for
most
voluntary muscle mass of the body and
Fig-5 Smooth muscle
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involuntary and is innervated by the
autonomic nervous system. Smooth muscle
is
widely
distributed
throughout
the
SKLETAL MUSCLE
An anatomically named muscle such as
deltoid muscle consists of many muscle
digestive tube, in the tubular portions of
bundle
or
fascicles
(Fig-8)
which
is
many organs and in the walls of many blood
surrounded by the connective tissue called
vessels.
as epimysium. Each muscle bundle consists
Unique terms are often used in describing
the component of muscle cells (Fig-6).
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Muscle membran is referred to as sarcolema,
restriction
the cytoplasm as sarcoplasm, the smooth
endoplasmic
reticulum
as
sarcoplasmic
Fig-8 Organization of skeletal muscle
reticulum and occasionally the mitochondria
of a variable number of muscle fibers
as sarcosomes. The muscle cells frequently
surrounded or delineated by the connective
tissue, the part of epimysium that extended
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inward, surrounding the muscle bundles or
fascicles called as
restriction
perimysium. Muscle
fiber is the basic structural unit of skeletal
Fig-6 The Organels of muscle fiber
muscle composed by a long, cylindrical and
are called as muscle fiber because they are
multinucleate structure. The muscle fiber is
much longer than they are wide. Unlike the
surrounded by the extension of connective
collagen fibers however they are living
tissue, the perimysium inward called as
entities.
endomysium.
All three muscle types are derived from
All of the connective tissue conducts the
mesoderm. Cardiac muscle originates in
blood vessels, lymphatic vessels, and nerve
splanchnopleuric mesoderm most smooth
into the interior of the muscle, bringing them
muscle is derivated from splanchnic and
close to the individual muscle fibers.
somatic
mesoderm, and
most
skeletal
muscles originate from somatic mesoderm.
Muscle fiber (Fig-6 and 9) is a long,
multinucleated and cylindrical structure with
1-40 mm in long and 10-100 mikrometer in
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wide. Numerous nuclei, space along the
restriction
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Fig-7 Skeletal, smooth and cardiac muscle
restriction
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Fig-9 The muscle fiber
THE LIGHT MICROSCOPY OF
length of the fiber are displaced to the
periphery by the column of myofibril that
SKELETAL MUSCLE FIBER
In the light microscopy, the hemato
occupies the bulk of the sarcoplasm. They
xyllin-eosin
are flattened against the sarcolemma. The
illustrates alternate light and dark transverse
cytoplasmic surface of the sarcolemma in
binding along the fibers. The hematoxyllin
skeletal muscle is coated with the 400 kD
stainned dark bands (Fig-9and 10) are
protein dystrophin which appears to provide
known
mechanical reinforcement to the membrane,
biferingent/double refractile with polarized
thereby
protecting
it
against
as
stained
A
striated
bands
muscle
(anisotropic
or
stresses
developed during muscular contraction.
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All of the common cell organelles (Fig-6
restriction
and 9) are represented in the sarcoplasm,
such as Golgi complex, mitochondria ect.
The
sarcoplasm
also
contains
the
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restriction
myoglobin, an oxygen binding protein
which is largely responsible for the slightly
Fig-10 The dark (A) and light (I) bands
brown color of muscle. Myoglobin is
light) with approximately 1.5 um in length,
present in low concentration and it possibly
while the alternate bands that do not
of little functional significance in the
stainned with hematoxyllin-eosin are the I
relatively pale muscles of humans. As
bands (isotropic or singly
required,
from
polarized light) with approximately 1 um in
myoglobin and becomes available for
length. The center of each A band is
oxidations.
occupied by a pale area, the H band, which
oxygen
dissociates
refractile with
The interior of muscle fiber (Fig-9)
is bisected by a thin M line. The I bands is
contains a variable number of longitudinally
bisected by a thin dark line, the Z disk (Z
oriented structural units called as myofibril
line) . The region of the myofibril between
with usually range from 1 to 2 mikrometer
two successive Z disks, known as a
in diameter. Myofibril consists of many
sarcomere, is 2.5 um in length and is
myofilament (more than 100) which are
considered to be the contratile unit of
oriented longitudinally within the myofibril.
skeletal muscle fibers (Fig-10).
There are two types of myofilament; the
thick and thin.
The term sarcomer refers to the unit of
distance between adjacent Z lines and is the
fundamental unit of contraction.
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In a relaxed skeletal muscle fiber (Fig. 9-
overlap
between
the
two
groups
of
10), the thick filaments do not extend the
filaments, effectively reducing the width of
entire length of the sarcomere, whereas the
the I and H bands without influencing the
width of the A band.
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The arrangement of the thick and thin
filaments bears a specific and constant
restriction
relationship. In mammalian skeletal muscle
each
thick
filament
is
surrounded
thin filaments projecting from the two Z
equidistantly by six thin filaments (Fig. 9-
disks of the sarcomere meet in the midline.
10). Cross-sections through the region of
Therefore, there are regions of each
over-lapping thin and thick filaments display
sarcomere, on either side of each Z disk,
a hexagonal pattern, with a thick filament is
where only thin filaments are present,
surrounded by six thin filaments.
known as I band which can be seen by the
light microscopy. The region of each
ULTRASTRUCTURE
sarcomere that encompasses the entire
MUSCLE FIBER
OF
STRIATED
length of the thick filaments is the A band.
The fine structure of the sarcolemma is
The zone in the middle of the A band, which
similar to that of other cell membranes.
is devoid of thin filament, is the H band. As
However the distinguishing feature of this
noted earlier, the H band is bisected by the
membrane is that it is continued within the
M line, which consists of myomesin, C
skeletal muscle fiber as numerous T tubules
protein, and other proteins that interconnect
(transverse tubules). T-tubules (Fig.8 and
thick filaments to maintain their specific
11) is a long, tubule extending inward from
lattice arrangement.
the sarcolemma that penetrate deep into the
During muscle contraction (Fig-9,10) the
various
transverse
characteristically.
bands
During
behave
interior of the muscle fiber crossing many
myofibrils.
contraction
T tubules pass transversely across the
individual thick and thin filaments do not
fiber and lie specifically in the plane of the
shorten, instead, the two Z disk are brought
junction of the A and I bands in mammalian
closer together as the thin filaments slide
skeletal muscle. One sarcomere has two sets
past the thick filaments (sliding filaments
of T tubules; one at each interface of the A
theory). Thus when contraction occurs, the
and I bands. T-tubules extend deep into the
motion of the thin filaments toward the
interior of the fiber and facilitate the
center of the sarcomere creates a greater
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conduction of waves of depolarization along
and vimentin (Fig.12) which secure the
the sarcolemma.
periphery of the Z disks of neighboring
Sarcoplasmic reticulum (Fig. 8 and 11) is
myofibrils to each other. These bundles of
a membrane-bounded tubules that form a
myofibrils are attached to the cytoplasmic
continuous network occupying the narrow
aspect of the sarcolemma by various
spaces between the myofibrils throughout
proteins, including dystrophin, a protein that
the muscle fiber. Although it corresponds to
binds to actin.
the endoplasmic reticulum of other cells, it
Deep to the sarcolemma, and inter-
is largely devoid of associated ribosome and
spersed between and among myofibrils are
is specialized for a different function. The
numerous
sarcoplasmic reticulum forms a meshwork
many
around each myofibril and displays dilated
Moreover,
terminal cisternae at each A-I junction. Thus
located just deep to the sarcoplasm.
elongated
highly
mitochondria
interdigitating
numerous
with
cristae.
mitochondria
are
two of these cisternae are always in close
apposition to a T-tubule forming a Triad in
STRUCTURAL ORGANIZATION OF
which a T tubule is flanked by two cisternae.
MYOFIBRILS
This arrangement permits a wave of
depolarization
to
spread,
almost
instantaneously, from the surface of the
Electron microscopy demonstrates the
presence of parallel, interdigitating thick and
thin rod-like myofilaments.
sarcolemma throughout the cell, reaching
the terminal cisternae, which have voltage-
THICK FILAMENT
gated Ca2+ release channel.
The thick filaments (15 nm in diameter
The sarcoplasmic reticulum regulates
muscle
contraction
by
controlled
and 1.5 um long) are composed of myosin.
These
filaments
form
parallel
arrays
sequestering (leading to relaxation) and
interdigitating with the thin filaments in a
release (leading to contraction) of Ca2+ ions
specific fashion.
within the sarcopalsm. The wave of
filament is slightly wider in the middle than
depolarization transmitted by T tubules
at either end.
triggers the opening of the calcium release
The myosin thick
Every thick filament consists of 200 to
channels of the terminal custernae, resulting
300
in release of calcium into the cytosol in the
molecule (150 nm long; 2 to 3 nm in
vicinity of the myofibrils.
diameter) is composed of two identical
Myofibrils are held in register with each
other by the intermediate filament desmin
myosin
molecules.
Each
myosin
heavy chains and two pairs of light chains.
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The heavy chains resemble two golf
clubs, whose rod-like polypeptide chains are
THE THIN FILAMENT
wrapped around each other in an alpa-helix.
The thin filaments (7nm in diameter
The heavy chains can be cleaved by trypsin
and 1.0um long) are composed primarily of
into a rod-like tail, light meromyosin, and a
actin (Fig-13).
globular head, heavy meromyosin. Heavy
Thin filaments originate at the Z disk
meromyosin is cleaved by papain into two
and project toward the center of the two
globular (S1) moieties and a short, helical,
adjacent
rod-like segment (S2) (Fig-13). The S1
opposite directions. A single sarcomere will
subfragment binds adenosine triphosphate
have two groups of parallel arrays of thin
(ATP) and functions in the formation of
filaments, each attached to one Z disk. All of
cross-bridges
these filaments point toward to the middle of
between
thick
and
thin
myofilaments. The heavy chains has two
sarcomeres,
thus
pointing
in
the sarcomere (Fig-13).
hinges at two different regions: one is at the
The major component of each thin
junction of the LMM and HMM, and the
filament is F-actin, a polymer of globular G-
other is at the neck region near the two
actin unit. Although G-actin molecules are
globular heads (Fig-14).
globular, they all polymerize in the same
Light chains are of two types,and one of
spatial orientation, imparting to the filament
each is associated with each S1 subfragment
a distinct polarity. The plus end of each
of the myosin molecule. Each heavy chain
-actinin,
has two light chains, and a myosin molecule
the minus end extends toward the center of
is composed of two heavy chains and four
the sarcomere. Each G-actin molecule also
light chains.
contains an active site where the head region
The 200-300 myosin molecule in a thick
(S1 subfragment) of myosin binds. Two
filament are bundle together such that one
chains of F-actin are wound around each
half of the molecules have their heads
other in a tight helix (36-nm periodicity) like
pointing toward the opposite end (Fig-14).
two strands of pearls (Fig-13).
This arrangement result in a bare zone in the
There are shallow grooves along the
center of the A band where there are no
length of the F-actin double-stranded helix.
myosin heads. This molecule organization
Pencil-shaped like tropomyosin molecules
explains in part why two sets of thin
about 40 nm long, polymerize to form head-
filaments in a sarcomere are pulled together
to-tail filaments that occupy the shallow
toward each other that is toward the center
grooves in the actin filaments. Bound
of the A band .
tropomyosin masks the active sites on the
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actin molecules by partially overlapping
disk and ensuring the maintenance of the
them (Fig-13).
specific array (Fig-13).
Approximately 25 to 30 nm from the
beginning of each tropomyosin molecule is a
MUSCLE
single
RELAXATION
troponin
molecule
(Fig.13-15),
composed of three globular poly peptides,
CONTRACTION
Contraction
effectively
AND
reduces
the
TnT, TnC, and TnI. The TnT subunit binds
resting length of the muscle fiber by an
the entire troponin molecule to tropomyosin;
amount that is equal to the sum of all
TnC has a great affinity for calcium; and TnI
shortenings that occur in all sarcomeres of
binds to actin, preventing the interaction
that particular muscle cell. The process of
between actin and myosin (Fig-16)
contraction, usually triggered by neural
Binding of calcium by TnC induces a
conformational
shift
in
impulses, obeys the “all-or-none law”in that
tropomyosin,
a single muscle fiber will either contract or
exposing the previously blocked active sites
not contract as a result of stimulation. The
on the actin filament, so that myosin heads
strength of contraction of a gross anatomical
can bind.
muscle, such as the biceps, is a function of
The structural organization of myofibrils
the number of muscle fibers that undergo
is maintained largely by three proteins, titin,
contraction. The stimulus is transferred at
actinin, and nebulin. Thick filaments are
the neuromuscular junction. During muscle
positioned precisely within the sarcomere
contraction the thin filaments slide past the
with the assistance of titin, a large, linear,
thick filaments, as proposed by Huxleys
elastic protein (Fig-13). A titin molecule
sliding filament theory.
extends from each half of a thick filament to
The following sequence of the events leads
the adjacent Z disk, thus anchoring the
to contraction in skeletal muscle:
filaments between the two Z disks of each
1. Impulse,
generated
along
the
sarcomere. Thin filaments are held in
sarcolemma, is transmitted into the
register
protein
interior of the fiber via the tubules,
, a component of the Z disk that
where it is conveyed to the terminal
by
the
rod-shaped
can bind thin filaments in parallel arrays
cisternae
(Fig-13). In addition, two molecules of
reticulum(see Fig-8,11).
nebulin-a
long,
nonelastic
protein-are
2. Calcium
of
ions
the
leave
sarcoplasmic
the
terminal
wrapped around the entire length of each
cisternae through voltage-gated calcium-
thin filament, further anchoring it in the Z
release channels, enter the cytosol, and
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bind to the TnC subunit of troponin,
once the stimulation impulses cease, muscle
altering its conformation (Fig-16)
relaxation occurs involving a reverssal of the
3. Conformational
change
in troponin
step that led to contraction. Fisrt calcium
shifts the position of tropomyosin
pump in the membrane of the sarcoplasmic
deeper into the groove, unmasking the
reticulum actively drive Ca2+ back into the
active site(myosin-binding site) on the
terminal cisternae, where the calcium ions
actin molecule (Fig-16)
are bound by the protein calsequestrin. The
4. ATP present on the S1 fragment of
myosin
is
hydrolyzed,
adenosine
diphosphate
inorganic
phosphate
but
both
TnC to loose its bound Ca2+, tropomyosin
(ADP)
and
then reverts to the position in which it masks
remain
the active site of actin, preventing the
(P1)
attached to the S1 fragment, and the
complex binds to the active site on
actin(Fig-16).
5. P1 is released, resulting not only in an
increased bond strength between the
actin and myosin but also in a
conformational alteration of the S1
fragment.
6. ADP is also released, and the thin
filament is dragged toward the center of
the sarcomere(“power stroke”).
7. A new ATP molecule binds to the S1
fragment, which causes the release of
the bond between actin and myosin.
The attachment and release cycles must be
repeated numerous times for contraction to
be completed. Each attachment and release
requires ATP for the conversion of chemical
energy into motion.
As
long
as
reduced level of Ca2+ in the cytosol cause
cytosolic
calcium
concentration remains high enough, actin
filament will remain in the active stateand
contraction cycles will continue. However
interaction of actin and myosin.