2. Introduction
• Muscle is generally divided into three types: skeletal, cardiac,
and smooth
• About 40 % of the body is skeletal muscle; another 10 % is
smooth and cardiac muscle
• Excitable tissues that are excited chemically, electrically, and
mechanically to produce an AP that is transmitted along their
cell membranes
• Skeletal & cardiac muscles have cross striations whereas
smooth muscles does not
• Skeletal one does not contract in the absence of nervous
stimulation whereas cardiac & unitary type smooth ones are
functionally syncytial; the later two can be modulated by ANS
• The multiunit type smooth muscles found in the eye and in
some other locations is not spontaneously active and
resembles skeletal muscle in graded contractile ability
3. Skeletal Muscle Morphology
• Muscle tissue is made up of a large number of
individual muscle cells or myocytes
• They are called muscle fibers due to their long and
slender appearance
• They are multinucleated; arranged parallel to one
another, thus, giving additive action on the force of
contraction of the unit
• Most skeletal muscles begin and end in tendons
• Muscle tissue is separated from the neighboring
tissues by a thick fibrous tissue layer known as fascia
• Beneath the fascia, muscle is covered by a connective
tissue sheath called epimysium
4. • In the muscle, the muscle fibers are arranged in
various groups called bundles or fasciculi
• Each fasciculus is covered by a connective sheath
called perimysium
• Endomysium is a connective tissue layer that cover
each muscle fiber
• In most skeletal muscles, each fiber extends the
entire length of the muscle
• Except for about 2 % of the fibers, each fiber is
usually innervated by only one nerve ending,
located near the middle of the fiber
5.
6. Muscle Fiber (MF)
• Each muscle cell or MF is cylindrical in shape with
average length of 3 cm (1-4cm) & diameter from 10
µ to 100 µ
• MFs are attached to tendon (a tough cord of CTs)
which is, in turn, attached to the bone
• Each MF is enclosed by a plasma membrane, that
lies beneath the endomysium; also called
sarcolemma & cytoplasm is known as sarcoplasm
• Each MF contains several hundred to several
thousand myofibrils, which are demonstrated by
the many small open dots in the cross-sectional
view
7. • Each myofibril is divisible into individual
myofilaments (about 1500 adjacent myosin
filaments and 3000 actin filaments) which contain
several proteins that together make up the
contractile machinery of the skeletal muscle
• The contractile mechanism in skeletal muscle
largely depends on the proteins myosin-II, actin,
tropomyosin, and troponin
• Troponin is made up of three subunits: troponin I,
troponin T, and troponin C
• Other proteins are involved in maintaining the
above contractile proteins in appropriate structural
relationship to one another and to the ECM
8. Striations
• When a MF is studied under the light microscope, it
will show characteristic striations which are due to
differences in the refractive indexes of the various
parts of the MF under microscope
• These striations occur as a number of two alternat-
-ting bands; light & dark bands
• Light band is called ‘I’ (isotropic) band because it
is isotropic to polarized light
• Dark band is called ‘A’ (anisotropic) band because it
is anisotropic to polarized light
• These bands appear due to myofilaments; myosin
(thick) & actin (thin) which partially interdigitate
9. • The light or I bands contain only actin filaments
• The dark bands contain myosin filaments, as well as
the ends of the actin filaments where they overlap
the myosin
• I band is divided into two portions, by means of
a narrow and dark line called ‘Z’ line or ‘Z’ disk (in
German, zwischenscheibe = between disks)
• ‘Z’ disk is composed of filamentous protein that
passes crosswise across the myofibril and also from
myofibril to myofibril, attaching the myofibrils to
one another all the way across the muscle fiber
• Therefore, the entire muscle fiber has light and dark
bands, as do the individual myofibrils
10. • The portion of myofibril in between two ‘Z’ lines is
called sarcomere
• the ends of the actin filaments are attached to Z
disc; from where these filaments extend in both
directions to interdigitate with the myosin filaments
• In the middle of ‘A’ band, there is a light area called
‘H’ zone (H = hell = light – in German, H = Henson –
discoverer)
• In the middle of ‘H’ zone lies the middle part of
myosin filament
• This is called ‘M’ line (in German-mittel = middle).
‘M’ line is formed by myosin binding proteins
11.
12.
13.
14. • During the contraction, the
actin filaments glide down
between the myosin
filaments towards the center
of ‘H’ zone and approach the
corresponding actin filaments
from the next ‘Z’ line
• The ‘Z’ lines also approach
the ends of myosin filaments,
so that the ‘H’ zone and ‘I’
bands are shortened during
contraction
• During the relaxation
of the muscle, the actin
fiaments and ‘Z’ lines come
back to the original position
15. Contractile Elements:(Proteins) Of Muscle
• Myosin filaments are formed by myosin molecules
• Actin filaments are formed by three types of
proteins called actin, tropomyosin and troponin
• These four proteins together constitute the
contractile elements of the muscle
• MYOSIN MOLECULE:
• Each myosin filament consists of about 200 myosin
molecules
• Only myosin II is present in the sarcomere
• Myosin II is a globulin with a MW of 480,000
• Each myosin molecule is made up of 6 polypeptide
chains; two are heavy and four are light chains
16. • MW of each heavy chain is 200,000 (2 × 200,000 =
400,000) & that of each light chain is 20,000 (4 ×
20,000 = 80,000) giving MW of 480,000 for myosin
• Each myosin has two globular heads and a long tail
• The tail is made up of two heavy chains, which twist
around each other in the form of a double helix
• At the end of the double helix, both the heavy
chains turn away in opposite directions
• Amino terminal portions of each heavy chain along
with two light chains form the globular head
• These heads contain an actin-binding site and a
catalytic site that hydrolyzes ATP
17. • Myosin head is absent in the central part of myosin
filament, i.e. in the ‘H’ zone
• ACTIN MOLECULE:
• Major constituents of the thin actin filaments
• Each actin molecule is called F-actin and it is the
polymer of a small protein known as G-actin
• There are about 300 to 400 actin molecules in each
actin filament
• The molecular weight of each molecule is 42,000
• The actin molecules in the actin filament are also
arranged in the form of a double helix
• Each F-actin molecule has an active site to which
the myosin head is attached
18. • TROPOMYOSIN:
• About 40 to 60 tropomyosin molecules are situated
along the double helix strand of actin filament
• Long filaments located in the groove between the two
chains in the actin
• MW of each tropomyosin molecule is 70,000
• In relaxed condition of the muscle, the tropomyosin
molecules cover all the active sites of F-actin
• TROPONIN:
• Small globular molecules located at intervals along the
tropomyosin; has three subunits:
• 1. Troponin T binds the troponin to tropomyosin
• 2. Troponin I (-) the interaction of myosin with actin
• 3. Troponin C binds with Ca2+ to initiate contraction
20. • In addition to the contractile proteins, the sarcomere
contains several other proteins such as:
• 1. Actinin, which attaches actin fiament to ‘Z’ line
• 2. Desmin, which binds ‘Z’ line with sarcolemma
• 3. Nebulin, which runs in close association with and
parallel to actin fiaments
• 4. Titin, a large protein connecting ‘M’ line and ‘Z’ line;
forms scaffolding (framework) for sarcomere & giving
elasticity to the muscle; When the muscle is stretched,
the titin unfolds itself & if the stretching is more, it
offers resistance and protects the sarcomere from
overstretching
• Dystrophin, a rod-shaped large protein that connects
actin filament to dystroglycan, a TM protein, present in
the sarcolemma; form dystrophin-dystroglycan complex
21. Sarcotubular System of Muscle Fiber
• Myofibrils of each muscle fiber are suspended side by
side in the muscle fiber
• They are surrounded by structures made up of
membranes that appear in electronmicrographs as
vesicles and tubules
• These structures form the sarcotubular system, which
is made up of a T-system and a sarcoplasmic reticulum
• The T system of transverse tubules are narrow tubules
formed by the invagination of the sarcolemma and
forms a grid perforated by the individual muscle fibrils
• Because of their origin from sarcolemma, the T-tubules
open to the exterior of the muscle cell & hence, the ECF
runs through their lumen
22. • The sarcoplasmic reticulum (SR) is composed of closed
longitudinal tubules around each myofibril that run in
long axis of the muscle fiber
• SR correspond to the ER of other cells
• At regular intervals, throughout the length of the
myofibrils, SR tubules dilate to form a pair of lateral
sacs called terminal cisternae
• Each pair of terminal cisternae is in close contact with
T-tubule
• The T-tubule along with the cisternae on either side is
called the triad of skeletal muscle
• In human skeletal muscle, the triads are situated at
the junction between ‘A’ band and ‘I’ band
• Ca2+ are stored in SR and the amount of Ca2+ is more in
cisternae
23. • The T system
provides a path for
the rapid trans-
-mission of the AP
from the cell
membrane to all the
fibrils in the muscle
• The SR also
participates in
muscle metabolism
24.
25. Electrical Characteristics
Of Skeletal Muscle
• Electrical events occur in the muscle during resting
condition as well as active conditions
• Electrical potential in the muscle during resting
condition is called RMP
• The skeletal muscle contract following AP; the stages of
AP are similar to nerve AP with quantitative differences
• The AP lasts 2–4 ms and is conducted along the muscle
fiber at about 5 m/s
• The absolute refractory period is 1–3 ms long, and the
after-polarizations, with their related changes in
threshold to electrical stimulation, are relatively
prolonged
26. Contractile Responses
• Muscle fiber membrane depolarization normally starts at the
motor end plate
• The AP is transmitted along the muscle fiber and initiates the
contractile response
• THE MUSCLE TWITCH:
• A single AP causes a brief contraction followed by relaxation;
this response is called a muscle twitch
• The twitch starts about 2 ms after the start of depolarization
of the membrane, before repolarization is complete
• The duration of the twitch varies with the type of muscle
being tested; “Fast” muscle fibers, primarily those concerned
with fine, rapid, precise movement, have twitch durations as
short as 7.5 ms & “slow” muscle fibers, principally those
involved in strong, gross, sustained movements, have twitch
durations up to 100 ms
27. Molecular Basis Of Contraction
• Molecular mechanism of muscle contraction
involves sliding of the thin filaments over the thick
filaments and includes three stages:
• 1. Excitation-contraction coupling
• 2. Role of troponin and tropomyosin
• 3. Sliding mechanism
• 1. Excitation-contraction Coupling:
• It is a process by which depolarization of the muscle
fiber initiates contraction
• The AP is generated in the muscle fiber when a
muscle is excited by the impulses via motor nerve
and NMJ
28. • AP spreads over sarcolemma and is is transmitted to all
the fibrils in the fiber via the T system
• It triggers the release of Ca2+ from the terminal
cisterns
• Depolarization of the T- tubule membrane activates the
SR via dihydropyridine receptors (DHPR), named for
the drug dihydropyridine, which blocks them
• DHPR are voltage-gated Ca2+ channels in the T tubule
• In cardiac muscle, influx of Ca2+ via these channels
triggers the release of Ca2+ stored in the SR (calcium-
induced calcium release) by activating the ryanodine
receptor (RyR)- a ligand gated Ca2+ channel with Ca2+
as its natural ligand
29. • However, in skeletal muscle, the DHPR that serves
as the voltage sensor unlocks release of Ca2+ from
the nearby SR via physical interaction with the RyR
• The released Ca2+ is quickly amplified & is also
reduced in the muscle cell by the SERCA pump
• The SERCA pump uses energy from ATP hydrolysis
to remove Ca2+ from the cytosol back into the
terminal cisterns, where it is stored until released
by the next AP
• Once the Ca2+ outside the reticulum has been
lowered sufficiently, chemical interaction between
myosin and actin ceases and the muscle relaxes
30. • 2. Role of Troponin and Tropomyosin:
• Normally, the head of myosin molecules has a
strong tendency to get attached with active site of
F-actin
• However, in relaxed condition, the active site of F-
actin is covered by the tropomyosin; so no
interaction of the myosin head with actin molecule
• On release of large number of Ca2+ from SR, it binds
with troponin C which lead to conformational
change in troponin, thus, pulling tropomyosin
molecule away from F-actin
• This action uncovers the active site of F-actin to
whom the head of myosin gets attached
immediately
31. • 3. Sliding Mechanism and Formation of
Actomyosin Complex – Sliding Theory
• Sliding theory explains cross-bridge interaction
between actin and myosin that brings about muscle
contraction by means of the sliding filament
mechanism; also called ratchet theory or walk along
theory
• The sliding during muscle contraction occurs when the
myosin heads bind firmly to actin, bend at the junction
of the head with the neck, and then detach
• This “power stroke” depends on the simultaneous
hydrolysis of ATP
• Myosin-II molecules are dimers that have two heads,
but only one attaches to actin at any given time
32. • Upon formation of the cross-bridge, ADP is
released, causing a conformational change in the
myosin head that moves the thin f lament relative
to the thick filament, comprising the cross-bridge
“power stroke.”
• ATP quickly binds to the free site on the myosin,
which leads to a detachment of the myosin head
from the thin filament
• ATP is hydrolyzed and inorganic phosphate (Pi )
released, causing a “re-cocking” of the myosin head
and completing the cycle
• As long as Ca2+ remains elevated and sufficient ATP
is available, this cycle repeats
