MUSCLE TISSUE

PHM-117
ANATOMY & HISTOLOGY
 Introduction
• The muscle tissue, like the
connective tissue, is also derived
from the mesenchyme.
• There are three types of muscle
tissues:
1. Skeletal muscles/striated
muscles
2. Cardiac muscles
3. Smooth muscles
• The cytoplasm of a muscle cell
(myocyte; Latin) is often named as
the sarcoplasm (Gr, Sarkos means
flesh), its endoplasmic reticulum is
termed as the sarcoplasmic
reticulum and its plasma
membrane is referred to as the
sarcolemma.
 Introduction

■ Depending upon their different

functional requirements, the
structure as well as the contraction
pattern and mechanism of the three
types of muscles greatly varies.
SKELETAL MUSCLE
Skeletal Muscle Cell Development
■ During embryonic development, the huge
skeletal muscle fibres are formed by the
fusion of many smaller cells called
myoblasts.
■ A striking feature is the presence of multiple
nuclei dispersed just beneath the plasma
membrane in a single muscle cell
 Organization
■ Following thin layers of connective tissue surround and organise the skeletal muscles.
1. The epimysium, an external sheath of dense irregular connective tissue, surrounds the
entire muscle. Septa of this tissue extend inward, carrying the larger nerves, blood
vessels, and lymphatics of the muscle.
2. The perimysium is a thin connective tissue layer that immediately surrounds each
bundle of muscle fibers termed a fascicle. Each fascicle of muscle fibers makes up a
functional unit in which the fibers work together. Nerves, blood vessels, and
lymphatics penetrate the perimysium to supply each fascicle.
3. Within fascicles a very thin, delicate layer of reticular fibers and scattered fibroblasts,
the endomysium, surrounds the external lamina of individual muscle fibers. In
addition to nerve fibers, capillaries form a rich network in the endomysium bringing
O2 to the muscle fibers.
■ All three layers plus the dense irregular connective tissue of the deep fascia, which
overlies the epimysium, are continuous with the tough connective tissue of a tendon at
myotendinous junctions which join the muscle to bone, skin, or another muscle.
Ultrastructural studies show that in these transitional regions, collagen fibers from the
tendon insert themselves among muscle fibers and associate directly with complex
infoldings of sarcolemma.
 Organization
• A skeletal muscle consists of a number of muscle cells, known as a myofibers (or simple muscle fibre), lying parallel to
one another and bundled together (fascicles) by connective tissue. The fibres usually extend the entire length of the muscle.
• A myofiber is relatively large, elongated, and cylinder shaped cell, measuring from 10 to 100 µm in diameter and up to
750,000 µm, or 2.5 feet, in length.
■ The sarcoplasm is highly organized, containing primarily long cylindrical filament bundles called myofibrils that run
parallel to the long axis of the fiber. The diameter of a myofibril is around 1-2 µm. The myofibrils appear to have
alternating light and dark bands.
 Organization
Whole Muscle
(An organ)

Muscle Fiber
(A cell)

Myofibril
(A specialized intracellular structure)

Thick and thin filaments

(Cytoskeletal elements)

Actin and myosin

(Protein molecules)
 • The sarcoplasm is highly organized,
Structure of Myofibrils containing primarily long cylindrical
filament bundles called myofibrils that
run parallel to the long axis of the fiber.
• The dark bands on the myofibrils are
called A bands (anisotropic or
birefringent in polarized light
microscopy); the light bands are called I
bands (isotropic, do not alter polarized
light).
• Each I band is seen to be bisected by a
dark transverse line, the Z disc (Ger.
zwischen, between). The repetitive Close observation of the A band shows the presence of a
functional subunit of the contractile lighter zone in its center, the H zone, corresponding to a
apparatus, the sarcomere, extends from Z region with only the rodlike portions of the myosin
disc to Z disc and is about 2.5-μm long in molecule and no thin filaments.
resting muscle. Bisecting the H zone is the M line (Ger. Mitte, middle),
• Light chains (actins) are bound with the containing a myosin-binding protein myomesin that holds
Z-discs through actin binding proteins the thick filaments in place, and creatine kinase.
called α-actinin.
 Structure of Myofibrils
• Single strands of a giant, highly
elastic protein known as titin
extend in both directions from
the M line along the length of
the thick filament to the Z lines
at opposite ends of the
sarcomere.
• Titin is the largest protein in the
body, being made up of nearly
30,000 amino acids.
• It serves as a scaffolding protein,
an elastic spring and participate
in complex cell signal
transduction during the
weightlifting induced muscle
development.
Structure of Myofibrils

■ With an electron microscope, fine cross

bridges can be seen extending from each
thick filament toward the surrounding thin
filaments in the areas where the thick and
thin filaments overlap.
■ Three-dimensionally, the thin filaments
are arranged hexagonally around the thick
filaments. Cross bridges project from each
thick filament in all six directions toward
the six surrounding thin filaments.
■ Each thin filament, in turn, is surrounded
by three thick filaments
■ A single muscle fiber may contain an
estimated 16 billion thick and 32 billion
thin filaments, all arranged in this precise
pattern within the myofibrils.
 • Mitochondria and sarcoplasmic
Structure of Myofibrils reticulum are found between the
myofibrils.
• 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, respectively, organized
within each myofibril in a symmetric
pattern containing thousands of each
filament type.
 Structure of Myofibrils
■ The thick myosin filaments are 1.6-μm long and 15-nm
wide; they occupy the A band at the middle region of the
sarcomere.
■ Myosin is a large complex (~500 kDa) with two identical
heavy chains and two pairs of light chains. Myosin
heavy chains are thin, rodlike motor proteins (150-nm
long and 2-3 nm thick) twisted together as myosin tails.
Globular projections containing the two myosin light
chains form a head at one end of each heavy chain.
■ The heads form the cross bridges between the thick and
thin filaments. Each cross bridge has two sites crucial to
the contractile process: (1) an actin-binding site and (2) a
myosin ATPase (ATP-splitting) site.
Structure of Myofibrils

■ The thin, helical actin filaments are each 1.0-μm long and 8-
nm wide and run between the thick filaments. Each G-actin
monomer contains a binding site for myosin.
■ The thin filaments have two tightly associated regulatory
proteins:
1. Tropomyosin, a 40-nm-long coil of two polypeptide
chains located in the groove between the two twisted
actin strands.
2. Troponin, a complex of three subunits: TnT, which
attaches to tropomyosin; TnC, which binds Ca2+; and
TnI, which regulates the actin-myosin interaction.
 T-Tubules
■ To trigger Ca2+ release from
sarcoplasmic reticulum throughout the
muscle fiber simultaneously and
produce uniform contraction of all
myofibrils, the sarcolemma has
tubular infoldings called transverse
or T-tubules. These long fingerlike
invaginations of the cell membrane
penetrate deeply into the sarcoplasm
and encircle each myofibril near the
aligned A- and I-band boundaries of
sarcomeres.
 T-Tubules

■ Adjacent to each T-tubule are expanded terminal cisternae of sarcoplasmic reticulum. This complex of
a T-tubule with two terminal cisternae is called a triad. The triad complex 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, which initiates contraction of sarcomeres.
 T-Tubules

■ Contraction is induced when an action potential arrives at a synapse, the neuromuscular junction
(NMJ), and is transmitted along the T-tubules to terminal cisternae of the sarcoplasmic reticulum to
trigger Ca2+ release.
Mechanism of Contraction
■ In a 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 cross-bridges to form.
■ Binding actin produces a conformational change or pivot
in the myosins, which pulls the thin filaments farther into
the A band, toward the Z disc.
Mechanism of Contraction

■ Energy for the myosin head pivot that pulls actin

is provided by hydrolysis of ATP bound to the
myosin heads, after which myosin binds another
ATP and detaches from actin.
■ In the continued presence of Ca2+ and ATP, these
attach-pivot-detach events occur in a repeating
cycle, each lasting about 50 milliseconds, which
rapidly shorten the sarcomere and contract the
muscle.
Mechanism of contraction

 Each myosin filament is a motor protein with two

heads that much resemble with the feet of kinesin
and dynein proteins.
 During the contraction of sarcomere, myosin
filaments do not move from their place but instead
these are the thin actin filaments that are pulled
from both sides of the sarcomere by the end-to-end
arranged thick myosin filaments.
 Each head of a myosin molecule has two active
sites:
1. Actin binding site
2. ATPase binding site
 Mechanism of contraction

 When the muscle is in relaxed position, the ATPase

binding site (which is enzymatic in nature) binds with
one ATP molecule and converts it into ADP and Pi. The
energy liberated results into the myosin heads to bend
at 45 degrees. However, the myosin head doesn’t bend
unless it is bound with the acting binding site. Hence, in
the absence of the activating signals, the myosin heads
remain ready for bending.
 Once that the nerve impulse reaches the neuromuscular
junction and the Ach is released on the sarcolemma, the
action potential is triggered in the sarcolemma that runs
throughout the muscle cell membrane.
 The transverse tubules (T tubules) have special proteins
on their surface that faces the gaps between the lateral
sacs (terminal cisternae) of the sarcoplasmic reticulum.
These proteins are called dihydropyridine receptors
(since these proteins are activated by dihydropyridine
drugs).
 Mechanism of contraction

 Likewise, the membrane of the terminal cisternae that

faces the gaps expresses foot proteins that are also
termed as ryanodine receptors.
 As the depolarization travels within the T Tubules, the
dihydropyridine receptors are activated that in turn
activate the ryanodine receptors on the terminal
cisternae. These terminal cisternae are the stores of
intracellular calcium ions and the ryanodine receptors
act as the channels for this calcium. Once these
ryanodine receptors are activated by the
dihydropyridine receptors on the T tubules, the calcium
efflux starts from the sarcoplasmic reticulum into the
sarcoplasm that surrounds the sarcomere.
 In the presence of calcium ions, the tronin binds with
calcium and shifts the orientation of tropomyosin in
such a way that the actin binding sites that were
previously covered by the tropomyosin are now exposed
to the myosin heads.
 Mechanism of contraction

 As soon as the myosin head binds with the actin binding site
on the thin filaments, the previously installed potential within
the myosin molecule bends the myosin head at 45 degrees,
pulling the actin filaments towards the center of the
sarcomere.
 The ADP and Pi are then released and a fresh ATP molecule
binds with the ATPase binding site that triggers the
detachment of the myosin head from the actin filament. At
the same time, the other myosin head binds with the actin
binding site and pulls the actin filament towards the center
sarcomere.
 If the calcium remains available, the myosin head that has
just detached from the actin head now binds with the other
actin molecule that comes next to the previous actin
molecule, pulling the actin filament towards the center of the
sarcomere. The process continues in such a manner that the
both myosin heads pull the actin filaments is the similar
fashion as we pull a rope by using two of our hands that pull
the rope one by one.
 Mechanism of contraction

 The time when one myosin head is pulling the actin

filament, the other myosin head remains detached and
the very next moment, the latter gets attached and the
former gets detached. Both heads never get attached
with actin molecule together at any given moment.
 Since the Ach that is released on the neuromuscular
junction is readily degraded, the action potential is
quickly reverted back to the normal resting membrane
potential in the absence of another nerve impulse. At
this moment, the T tubules stop firing, since the
membrane within these T tubules starts getting
repolarized and gains back its resting membrane
potential.
 Mechanism of contraction

 At this moment, the ryanodine receptors gets closed and

another protein SERC Pumps (sarcoplasmic/ endoplasmic
reticulum calcium ATPase Pumps) start moving calcium ions
from the sarcoplasm back into the terminal cisternae.
 Since the sytosolic calcium level declines, the troposin and
tropomyosin get back to their unexcited positions where the
actin binding sites are covered by the tropomyosin, blocking
any further interaction between myosin heads and actin
proteins. The thin filaments start moving towards the Z line
gradually and the muscle is now said to be relaxed.
 Rigor Mortis
o After a person dies, the sarcolemma does
not maintain the barrier between the
extracellular and intracellular calcium. The
calcium starts moving into the cytosol that
increases the intracellular calcium ion
concentration. Moreover, the calcium also
starts getting leaked from the terminal
cisternae.
o All these events result into the activation of
the muscles and the actin myosin
interaction starts taking place. However,
since the cells are dead and no more fresh
ATPs are synthesized by the mitochondria,
the myosin heads are not detached from the
actin heads and the muscles start getting
rigid.
o This process starts within 4 hours of death
and gets completed by 12 hours. The whole
phenomenon is termed as Rigor Mortis.
Mechanism of contraction
• Myelinated motor nerves branch out
within the perimysium, where each
nerve gives rise to several unmyelinated
terminal twigs that pass through
endomysium and form synapses with
individual muscle fibers.
• Each axonal branch forms a dilated
termination situated within a trough on
the muscle cell surface, which are part of
the synapses termed the neuromuscular
junctions, or motor end plates (MEPs).
As in all synapses the axon terminal
contains mitochondria and numerous
synaptic vesicles; here the vesicles
contain the neurotransmitter
acetylcholine. Between the axon and the
muscle is the synaptic cleft.
• Myelinated motor nerves branch out within the
perimysium, where each nerve gives rise to several
unmyelinated terminal twigs that pass through
endomysium and form synapses with individual
muscle fibers.
• Each axonal branch forms a dilated termination
situated within a trough on the muscle cell surface,
which are part of the synapses termed the
neuromuscular junctions, or motor end plates
(MEPs). As in all synapses the axon terminal contains
mitochondria and numerous synaptic vesicles; here the
vesicles contain the neurotransmitter acetylcholine.
Between the axon and the muscle is the synaptic cleft.
Mechanism of Muscle
Innervation
• Myelinated motor nerves branch out
within the perimysium, where each
nerve gives rise to several unmyelinated
terminal twigs that pass through
endomysium and form synapses with
individual muscle fibers.
• Each axonal branch forms a dilated
termination situated within a trough on
the muscle cell surface, which are part of
the synapses termed the neuromuscular
junctions, or motor end plates (MEPs).
As in all synapses the axon terminal
contains mitochondria and numerous
synaptic vesicles; here the vesicles
contain the neurotransmitter
acetylcholine. Between the axon and the
muscle is the synaptic cleft.
Mechanism of Muscle
Innervation
• Adjacent to the synaptic cleft, the sarcolemma
is thrown into numerous deep junctional
folds, which provide for greater postsynaptic
surface area and more transmembrane
acetylcholine receptors.
• When a nerve action potential reaches the
MEP, acetylcholine is liberated from the axon
terminal, diffuses across the cleft, and binds to
its receptors in the folded sarcolemma. The
acetylcholine receptor contains a
nonselective cation channel that opens upon
neurotransmitter binding, allowing influx of
cations, depolarizing the sarcolemma, and
producing the muscle action potential.
Movement of Bones
■ Human body contains around 600 skeletal muscles that control the movements of bones via their
contractions.
■ The bones are attached with the muscles via tendons. They may attach with a very distant bone
such as in fingers.
■ The number of fibers within a muscle varies greatly from a few hundred fibers (such as the delicate
eye muscle) to several hundred thousand fibers (such as in the leg muscles).
■ Typically, a muscle is attached with two bones at a joint. Since the muscle contraction can just pull
a bone (cannot push the same in the opposite direction), the movements of limb bones in the
opposite directions involve antagonistic pairs of muscles. The contraction of one muscle brings
two bones closer to one another (flexors) and the contraction of the other muscle moves the bones
apart (extensors).
■ For instance, the biceps act as flexors and the triceps act as the extensors of the arms.
Types of muscle contractions

■ Isotonic
■ Isokinetic
■ Isometric
■ Concentric and Eccentric
Generation of ATPs within the Muscle
Fibers
■ The muscle fibers need ATPs during the following four steps of the sarcomere contraction
process
1. Splitting of ATP by myosin ATPase provides the energy for the power stroke of the
cross bridge.
2. Binding (but not splitting) of a fresh molecule of ATP to myosin lets the cross bridge
detach from the actin filament at the end of a power stroke so that the cycle can be
repeated. This ATP is later split to provide energy for the next stroke of the cross
bridge.
3. Active transport of Ca2+ back into the lateral sacs of the SR during relaxation
depends on energy derived from the breakdown of ATP.
4. The ATP-dependent Na+–K+ pump actively returns the ions (Na+ back out of the cell
and K+ back into the cell) that moved during the generation of a contraction
inducing action potential in the muscle cell.
Generation of ATPs within the Muscle
Fibers
■ The muscle fibers generate ATPs by the following three mechanisms:
1. Creatine Phosphate mechanism
o Gives immediate supply of ATPs for the first 5 to 10 seconds of muscle contraction.

2. Oxidative phosphorylation
3. Glycolysis
Types of Skeletal Muscle Fibers
■ Slow oxidative (Type I) muscle fibers are adapted for slow contractions over long periods without
fatigue, having many mitochondria, many surrounding capillaries, and much myoglobin, all features
that make fresh tissue rich in these fibers dark or red in color. The examples include the postural
muscles of the back.
■ Fast oxidative (Type IIa) fibers have physiological and histological features intermediate between
those of the other two types. The examples include major muscles of legs.
■ Fast glycolytic (Type IIx) fibers are specialized for rapid, short-term contraction, having few
mitochondria or capillaries and depending largely on anaerobic metabolism of glucose derived from
stored glycogen, features which make such fibers appear white. Rapid contractions lead to rapid
fatigue as lactic acid produced by glycolysis accumulates. The examples include the extraocular
muscles.
• Time to peak twitch tension for the fast fibers is 15 to 40 msec, compared with the 50 to 100 msec peak twitch
tension time for the slow fibers. The two determining factors are the load and the myosin-ATPase activity of the
contracting fibers.
• Slow fibers are more resistant to fatigue than the fast fibers, because these fibers more efficiently utilize
nutrients (releasing 32 ATPs from 1 glucose molecule) as compared to the fast glycolytic fibers (that generate
just 2 ATPs from 1 glucose molecule). Accordingly, the slow fibers have dense supply of capillaries and more
mitochondria as compared to the slow fibers.
Types of Skeletal Muscle Fibers
Muscle Fatigue

■ Muscle fatigue is a protective mechanism to prevent a complete loss of ATPs from the muscle fibers.
■ The fatigue could be of two different origins
1. Muscle origin
2. Central origin
■ The fatigue with muscle origin may be due to the following reasons:
o An increase in inorganic phosphates
o Escape of calcium from the cells
o Depletion of glycogen
■ The fatigue with central origin may involve the following factors:
o Psychological factors due to the discomfort that a person feels during exercise
o Boredom and monotony that may affect physical performance
o An increased level of serotonin and tryptophane neurotransmitters in brain during central fatigue may be related
with the mechanism responsible for a decline in physical activity. However, the findings need further confirmation.
CARDIAC
MUSCLES
Cardiac Muscles

■ During embryonic development

mesenchymal cells around the primitive
heart tube align into chainlike arrays.
■ Rather than fusing into multinucleated
cells/fibers as in developing skeletal
muscle fibers, cardiac muscle cells
form complex junctions between
interdigitating processes.
■ Cells often branch and join with
adjacent fibers.
Cardiac Muscles ■ Mature cardiac muscle cells are
uninucleated, 15-30 μm in diameter and
85-120 μm long, with a striated banding
pattern comparable to that of skeletal
muscle.
■ Surrounding the muscle cells is a delicate
sheath of endomysium with a rich capillary
network.
■ A thicker perimysium separates bundles and
layers of muscle fibers and in specific areas
forms larger masses of fibrous connective
tissue comprising the “cardiac skeleton.”
■ A unique characteristic of cardiac muscle is
the presence of intercalated discs that
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
whereas the longitudinally oriented regions
of each intercalated disc run parallel to the
myofibrils and are filled with gap junctions
which provide ionic continuity between the
cells.
■ These regions serve as “electrical
synapses,” promoting rapid impulse
conduction through many cardiac muscle
cells simultaneously and contraction of
many adjacent cells as a unit.
Cardiac Muscles ■ Mitochondria occupy up to 40% of the cell
volume, higher than in slow oxidative skeletal
muscle fibers. Fatty acids, the major fuel of
the heart, are stored as triglycerides in small
lipid droplets. Glycogen granules as well as
perinuclear lipofuscin pigment granules may
also be present.
■ Muscle of the heart ventricles is much thicker
than that of the atria, reflecting its role in
pumping blood through the cardiovascular
system. T-tubules in ventricular muscle fibers
are well-developed, with large lumens and
penetrate the sarcoplasm in the vicinity of the
myofibrils’ Z discs. In atrial muscle T-tubules
are much smaller or entirely absent.
■ Sarcoplasmic reticulum is less well-organized
in cardiac compared to skeletal muscle fibers.
The junctions between its terminal cisterns
and T-tubules typically involve only one
structure of each type, forming profiles called
dyads rather than triads in TEM sections.
Cardiac Muscles ■ The cardiomyocytes have a special characteristic
of automaticity, that means these cells generate
their own action potential instead of depending
upon the nerve innervation. However, the
sympathetic and parasympathetic activation
modulates the cardiac activity by increasing or
decreasing the frequency of impulses
respectively.
■ The impulses are generated in the sinoatrial
node, which are later propagated to the
atrioventricular node, from where these impulses
are propagated to the whole ventricular muscle
mass through the His Purkinje fibers.
■ Secretory granules about 0.2-0.3 μm in diameter
are found near atrial muscle nuclei and are
associated with small Golgi complexes. These
granules release the peptide hormone atrial
natriuretic factor (ANF) which acts on target
cells in the kidney to affect Na+ excretion and
water balance. The contractile cells of the heart’s
atria thus also serve an endocrine function.
■ Calveoli are present on the cell
Smooth Muscles
membrane that contain ion channels.
■ Sarcoplasmic reticulum is there but
the calcium storage is much lesser as
compared to the striated muscles.
■ The nuclei are centralized, the ends of
the cells are tapering, much of the
mitochondria are located near the
nucleus.
■ The cytoplasmic dense bodies that
are loosely bound with sarcolemma
contain proteins, including α-actinin
that serves as Z-disk.
■ The contraction mechanism is slightly
different, as the actin filaments are
not attached with the tropomyosin
and troponin. These cells use calcium
calmodulin MLCK (myosin light
chain kinase) mechanism to activate
actin myosin cross bridges.
Introduction
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