CONTRACTION OF SKELETAL MUSCLE

PHS 201

• BY

DR MARKBERE ONIZIBE
Skeletal Muscle Fibre
• Muscle consists a number of muscle fibers lying
parallel to one another and held together by
connective tissue
• Single skeletal muscle cell is known as a muscle
fiber
• – Functional Unit of Skeletal Muscle
• – Length varies from few mm to many cm.
• – Diameter of 10 to 100 micron
– Multinucleated
– Large, elongated, and cylindrically shaped
– Fibers usually extend entire length of muscle
– Like other cells , MF contains mitochondria,
microsomes and endoplasmic reticulum etc
• Each Muscle Fiber is surrounded by a plasma membrane
called SARCOLEMMA.
• Individual MF is enveloped by layer of connective tissue
called ENDOMYSIUM ( which lies outside Sarcolemma)
• Several MF are enveloped together by another connective
tissue called PERIMYSIUM
• The entire Muscle is covered all round by EPIMYSIUM.
• ( Sarcolemma—Endomysium– Perimysium– Epimysium)
• Actin forms the major part of thin filaments.
– The thin filaments give rise to I- bands
– Actin occurs in two forms
• G-Actin ( Globular monomer)
– Each molecule contains one molecule of ATP
– Molecular weight of about 43000.
• F-Actin ( Globular monomer)
– Fibrous, thickness of 6-7 nm, polymerized G-Actin,
contains ADP.
– Polymerization occurs in presence of Calcium or
Magnesium ions
• Myosin
– Found in Thick Filaments
– Mol Weight of about 460,000.
– Chief Actin Binding Constituent.
– Hexamer containing two identical heavy chains
and 4 light chains.
• Troponin
– Troponin –C
– Can bind an release Calcium Ions.
– Troponin-I
– Exerts an inhibitory action over Actin-Myosin interaction
when Troponin C is without Calcium.
– Troponin T
– Serves to bind Troponin C and Troponin I subunits with
Tropomyosin-Actin Complex.
• (Troponin complex is found only in Striated Muscle)
Structure of Skeletal Muscle
• Myofibrils
• – Contractile elements of muscle fiber
• – Regular arrangement of thick and thin filaments
• •Thick filaments – myosin (protein)
• •Thin filaments – actin (protein)
 – Viewed microscopically myofibril displays
alternating dark (the A bands) and light bands (the I
bands) giving appearance of striations
• – Light bands , Only Actin, Isotropic to polarized
light-thus I-Bands.
• – Dark bands, Mainly myosin, Anisotropic to polarized
light-Thus A-Bands
• Sarcomere
– Functional unit of skeletal muscle
– Found between two Z lines (connects thin filaments of two
adjoining sarcomeres)
– Regions of sarcomere
• A band – Made up of thick filaments along with portions of
thin filaments that overlap on both ends of thick filaments
• H zone
– Lighter area within middle of A band where thin filaments do
not reach
• M line
– Extends vertically down middle of A band within center of H
zone
• I band
– Consists of remaining portion of thin filaments that do not
project into A band
Myosin

• Component of thick filament

• Composed of SIX polypeptide
chains, two identical heavy
chains, and four light chains.
• The two heavy chains wrap
spirally around each other to
form a double helix; however
one end of each of these chains is
folded into a globular protein
mass called the head; the
elongated portion is called the
tail.
• Tails oriented toward center of filament and globular heads
protrude outward at regular intervals
– Heads form cross bridges between thick and thin filaments
• Cross bridge has two important sites critical to contractile
process
– An actin-binding site
– A myosin ATPase (ATP-splitting) site
Cross Bridges in Myosin Filaments

• The protruding arms and heads together are called cross-

bridges.
•Each cross-bridge is believed to be flexible at two points
called hinges.
• One where the arm leaves the body of the myosin filament.
• Where the two heads attach to the arm.
ATPase activity of Myosin Head
• Another feature of myosin head, essential for muscle
contraction is that it functions as an ATPase enzyme.

• This property allows the head to cleave ATP and to use

the energy to energize the contraction.
 Actin

• Primary structural component of thin filaments

• Spherical in shape
• Thin filament also has two other proteins
– Tropomyosin and troponin
• Each actin molecule has special binding site for attachment
with myosin cross bridge
• – Binding results in contraction of muscle fiber
 The Actin Filament
• The back bone of the actin filament is a double stranded
• F-Actin protein molecule.
• Each strand of double F-actin helix is composed of
polymerized G-actin molecules.
• Attached to each one of the G-actin molecules is one
molecule of ADP. It is believed that these ADP molecules are
the active sites on the actin filaments with which the cross-
bridges of the myosin filaments interact to cause muscle
contraction.
• A pure actin filament without the presence of
• troponin-tropomyosin complex binds strongly with myosin
molecules, in the presence of Magnesium and ATP.
• However if the troponin-tropomyosin complex is added to
the actin filament, this binding does not take place.
• Thus the active sites on the normal actin filament of
relaxed muscle are inhibited or actually physically
covered by the troponin- tropomyosin complex.
• For contraction to take place the inhibitory effect of
the T-T complex must itself be inhibitted
 Large amount of Calcium Ion

• In the presence of large amounts of calcium ions the

inhibitory effect of T-T complex is inhibited.
• Calcium ion combines with troponin-C, the Troponin
complex undergoes conformational change that moves it
deeper into the groove between the two actin strands.
• This uncovers the active sites of the actin , thus allowing the
contraction to proceed
TROPOMYOSIN AND TROPONIN
• Often called regulatory proteins
• Tropomyosin
• – Thread-like molecules that lie end to end alongside groove of actin
spiral
In this position, covers actin sites blocking interaction that leads to
muscle contraction
• Troponin
• – Made of three polypeptide units
• One binds to tropomyosin
• One binds to actin
• One can bind with Ca2+
Role of Calcium in Cross-Bridge Formation
• Cross-bridge interaction between actin and myosin brings
about muscle contraction by means of the “Sliding Filament
Mechanism.”
• Walk-Along Theory of Contraction
GENERAL MECHANISM OF MUSCLE
CONTRACTION
• The initiation and execution of muscle contraction occur
inthe following sequential steps.
• 1. An action potential travels along a motor nerve to its
endings on muscle fibers.
• 2. At each ending, the nerve secretes a small amount of the
neurotransmitter acetylcholine.
• 3. Acetylcholine acts on a local area of the muscle fiber
membrane to open acetylcholine-gated cation channels
through protein molecules floating in the membrane .
• The opening of acetylcholine-gated channels allows large
quantities of sodium ions to diffuse to the interior of the
muscle fiber membrane causing local depolarization that in
turn leads to the opening of voltage-gated sodium channels,
which initiates an action potential at the membrane.
• 5. The action potential travels along the muscle fiber
membrane in the same way that action potentials travel along
nerve fiber membranes.
• 6. The action potential depolarizes the muscle membrane, and
much of the action potential electricity flows through the
center of the muscle fiber. Here it causes the sarcoplasmic
reticulum to release large quantities of calcium ions
• 7. The calcium ions initiate attractive forces between the
actin and myosin filaments, causing them to slide alongside
each other, which is the contractile process.
• 8.
After a fraction of a second, the calcium ions are pumped
back into the sarcoplasmic reticulum by a Ca2+ membrane
pump and remain stored in the reticulum until a new muscle
action potential comes along; this removal of calcium ions
from the myofibrils causes the muscle contraction to cease
 Sliding Filament Mechanism

• Increase in Ca2+ starts filament sliding

• Decrease in Ca2+ turns off sliding process
• Thin filaments on each side of sarcomere slide inward over
stationary thick filaments toward center of A band during
contraction
• As thin filaments slide inward, they pull Z lines closer
together
• Sarcomere shortens
 Power Stroke
• Activated cross bridge bends toward center of thick filament,
“rowing” in thin filament to which it is attached
• Sarcoplasmic reticulum releases Ca2+ into sarcoplasm
• Myosin heads bind to actin
• Myosin heads swivel toward center of sarcomere (power
stroke)
• ATP binds to myosin head and detaches it from actin
• Hydrolysis of ATP transfers energy to myosin head
and reorients it

• Contraction continues if ATP is available and Ca2+

level in sarcoplasm is high
Sliding Filament Mechanism
• All sarcomeres throughout muscle fiber’s length
shorten simultaneously
• Contraction is accomplished by thin filaments from
opposite sides of each sarcomere sliding closer
together between thick filaments
 Relaxation

• Depends on reuptake of Ca2+ into sarcoplasmic

reticulum (SR)
• Acetylcholinesterase breaks down ACh at
neuromuscular junction
• Muscle fiber action potential stops When local action
potential is no longer present, Ca2+ moves back into
sarcoplasmic reticulum
 Rigor Mortis

• Rigidity caused by loss of all the ATP which is required to

cause the separation of the crossbridges from the actin
filament during the relaxation process.
• Thus, several hours after death the muscles of the body go
into a state of contracture, called “ Rigor Mortis”, i.e. the
muscle contracts and becomes rigid even without action
potential.
• The muscle remains in rigor until the muscle proteins are
destroyed by autolysis
 Sarcoplasmic Reticulum
• Modified endoplasmic reticulum
• Consists of fine network of interconnected compartments
that surround each myofibril
• Not continuous but encircles myofibril throughout its length
• Segments are wrapped around each A band and each I band
– Ends of segments expand to form saclike regions
– lateral sacs (terminal cisternae)
 Transverse Tubules
• T tubules
• Run perpendicularly from surface of muscle cell membrane
into central portions of the muscle fiber
• Since membrane is continuous with surface membrane –
action potential on surface membrane also spreads down into
T-tubule
• Spread of action potential down a T tubule triggers release of
Ca2+ from sarcoplasmic reticulum into cytosol
Skeletal Muscle Mechanics
• Muscle consists of groups of muscle fibers bundled
together and attached to bones
• Connective tissue covering muscle divides muscle
internally into bundles
• Connective tissue extends beyond ends of muscle to
form tendons
• – Tendons attach muscle to bone
 Muscle Contractions

• Contractions of whole muscle can be of varying strength

• Twitch
– Brief, weak contraction
– Produced from single action potential
– Too short and too weak to be useful
– Normally does not take place in body
•Two primary factors which can be adjusted to accomplish
gradation of whole-muscle tension
– Number of muscle fibers contracting within a muscle
– Tension developed by each contracting fiber
 Motor Unit

• Motor unit
• – One motor neuron and the muscle fibers it innervates
• Number of muscle fibers varies among different motor units
• Number of muscle fibers per motor unit and number of
motor units per muscle vary widely
– Muscles that produce precise, delicate movements contain
fewer fibers per motor unit
– Muscles performing powerful, coarsely controlled movement
have larger number of fibers per motor unit
Twitch Summation and Tetanus
• Twitch summation
• – Results from sustained elevation of cytosolic calcium
• Tetanus
• – Occurs if muscle fiber is stimulated so rapidly that it does
not have a chance to relax between stimuli
– Contraction is usually three to four times stronger than a
single twitch
 Muscle Tension
• Tension is produced internally within sarcomeres
• Tension must be transmitted to bone by means of connective
tissue and tendons before bone can be moved (series-elastic
component)
• Muscle typically attached to at least two different bones
across a joint
• – Origin
• End of muscle attached to more stationary part of skeleton
• – Insertion
• End of muscle attached to skeletal part that moves
 Types of Contraction

• Two primary types

– Isotonic
• Muscle tension remains constant as muscle changes length
– Isometric
• Muscle is prevented from shortening
• Tension develops at constant muscle length
Contraction-Relaxation Steps Requiring ATP

• Splitting of ATP by myosin ATPase provides energy for

power stroke of cross bridge
• Binding of fresh molecule of ATP to myosin lets bridge
detach from actin filament at end of power stroke so cycle
can be repeated
• Active transport of Ca2+ back into sarcoplasmic reticulum
during relaxation depends on energy derived from breakdown
of ATP
Energy Sources for Contraction
• Transfer of high-energy phosphate from creatine phosphate to
ADP
– First energy storehouse tapped at onset of contractile activity
• Oxidative phosphorylation (citric acid cycle and electron
transport system
– Takes place within muscle mitochondria if sufficient O2 is
present
• Glycolysis
– Supports anaerobic or high-intensity exercise
Muscle Fatigue

• Occurs when exercising muscle can no longer respond

to stimulation with same degree of contractile activity
• Defense mechanism that protects muscle from
reaching point at which it can no longer produce ATP
• Underlying causes of muscle fatigue are unclear
 Major Types of Muscle Fibers

• Classified based on differences in ATP hydrolysis and

synthesis
• Three major types
• – Slow-oxidative (type I) fibers
• – Fast-oxidative (type IIa) fibers
• – Fast-glycolytic (type IIb) fibers
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