Muscle

Physiology
David T. OLUWOLE
Department of Physiology
College of Health Sciences, CUAB
 Learning Outcomes Introduction
Upon successful completion of this lecture series, you  Muscle is an excitable tissue.

should be able to describe, identify, and/or explain:  The Specialized function of the muscle cells is

CONTRACTION
1. Structure and function of skeletal muscle, including
 Like Neurons, muscles cells can be excited chemically,
excitation-contraction coupling, sliding filament
electrically and mechanically to produce an ACTION
mechanism, force generation, and isometric versus
POTENTIAL that is transmitted along the cell
isotonic contractions.
membranes.
2. Structure and functions of the cardiovascular system,
 There are numerous muscles in the human body
including the mechanical and electrical properties of
performing many useful functions in day to day activities.
cardiac muscle function.
 The human body has over 600 muscles which perform
3. Structure and functions of smooth muscles including many useful functions and help us in doing everything in
contraction of smooth muscle day-to-day life.
 Classification of Muscle
 Muscles are classified by three (3) different methods, based on different factors:
1. Depending upon the presence or 3. Depending upon the situation.
2. Depending upon the control
absence of striations; the muscles
 Voluntary Muscle: Voluntary  Skeletal Muscle: Skeletal muscle is situated in
are divided into two groups:
muscle is the muscle that is association with bones forming the skeletal
 Striated Muscle: Striated muscle is
controlled by the will. Skeletal
the muscle which has a large system. Skeletal muscles are anchored to the
muscles are the voluntary
number of cross striations
muscles. These muscles are bones by the tendons.
(transverse lines). Skeletal muscle
and cardiac muscle belong to this
innervated by somatic nerves.  Cardiac Muscle: Cardiac muscle forms the
 Involuntary Muscle: Muscle that
category. musculature of the heart.
cannot be controlled by the will is
 Non-striated Muscle: Muscle
called involuntary muscle.  Smooth Muscle: Smooth muscle is situated in
which does not have cross-
Cardiac muscle and smooth association with viscera. It is also called
striations is called non-striated
muscle are involuntary muscles.
muscle. It is also called plain visceral muscle. Smooth muscles form the main
These muscles are innervated by
muscle or smooth muscle. It is
autonomic nerves. contractile units of wall of the various visceral
found in the wall of the visceral
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organs. organs.
 Skeletal Muscles
Structure
 Skeletal muscles are made up of individual muscles fibres

that are the building blocks of the muscular system

 Mostly begins and ends in tendons such that muscle fibres

are arranged in parallel between the tendinous ends

 Each muscle fibre is a single cell but multinucleated, long,

cylindrical and enveloped by cell-membrane (Sarcolemma)

 Muscle fibers are made up of myofibrils (Fine parallel

filaments present in sarcoplasm of the muscle cells).

 These filaments are majorly made up of contractile proteins

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Introduction

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Composition of skeletal muscle

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 Skeletal Muscles

Light Microscopic
Structure

Muscle fibre in cross-section. In this

section, the individual myofibrils which

make up the muscle fibre. Thin filament

in green and thick filament in reddish-

brown something

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 Brief Summary
 Skeletal muscle is composed of bundles of
elongated muscle fibres which are cylindrical
and multinucleated.
 Fibres show a characteristic banding pattern with cross-
striations of alternating light and dark bands.
 The light bands are divided by a Z disc (dark transverse
line).
 The functional subunit is known as the sarcomere, and
this extends between two Z discs.
 Muscle fibres are surrounded by supportive layers of
connective tissue:
 Endomysium – surrounds individual muscle fibres
 Perimysium – surrounds a bundle of muscle fibres,
forming a fascicle (functional unit)
 Epimysium – surrounds the entire muscle 8
Brief Summary

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Sarcomere in relaxed and Contracted State

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Structure of Muscle proteins

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 Sarcolemma
 Sarcolemma is the cell membrane that enveloped
each muscle fibre as a single cell but multinucleated,
long and cylindrical.
 The sarcolemma of skeletal and cardiac muscle has
deep invaginations (T-Tubule) which penetrate into
the muscle fibres.
 The T-tubules are short for transverse tubules,
opening into the sarcoplasmic reticulum at the so-
called terminal cisternae.
 The action potential which causes muscle
contraction propagates along the sarcolemma and
the T-tubules.
 The network of T-tubules allows the action potential
to propagate through the muscle cell much faster.
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 Transverse T-Tubule Action Potential
 The transverse tubules (T tubules) are connected to the  At rest, there are fewer positively charged particles on the
sarcolemma. inner side of the membrane compared to the outer side, and
 T-tubules permit rapid transmission of the action the membrane is described as being polarised.
potential into the muscle cell, and also play an  During an action potential, positively charged particles
important role in regulating cellular calcium (predominantly sodium and calcium ions) flow across the
concentration. membrane from the outside to the inside.
 The sarcoplasmic reticulum acts as a storage facility for  This reverses the normal imbalance of charged particles and
calcium ions (Ca2+), which are essential for muscle is referred to as depolarization.
contraction.  One region of membrane depolarizes adjacent regions, and
 When contraction of a muscle is needed, stimulation the resulting wave of depolarization then spreads along the
from a nerve or an adjacent muscle cell causes a cell membrane.
characteristic flow of charged particles across the cell  The polarization of the membrane is restored as potassium
membrane known as an action potential. ions flow back across the membrane from the inside to the
outside of the cell.
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 CONTRACTILE ELEMENTS (PROTEINS) OF MUSCLE

MYOSIN

 Thick filaments are made of many bonded units of the

protein myosin.
 Myosin is the protein that causes muscles to contract.
 Each myosin molecule has two portions:
 Tail portion  Thus the head portion has two parts. Two light chains are
 Head portion. attached to each part of the head portion of myosin molecule.
Tail portion of myosin molecule  Each myosin head has two attachment sites.
 It is made up of two heavy chains, which twist around  One site is for actin filament and the other one is for one ATP
each other in the form of a double helix. molecule.
Head portion of myosin molecule  Myosin head is absent in the central part of myosin filament,
 At one end of the double helix, both the heavy chains i.e. in the ‘H’ zone.
turn away in opposite directions and form the globular
head portion.
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 CONTRACTILE ELEMENTS (PROTEINS) OF MUSCLE

ACTIN TROPOMYOSIN

 Actin molecules are the major constituents of the thin  Tropomyosin is a long protein fiber that wraps around actin and covers
the myosin-binding sites on actin in relaxed condition of the muscle
actin filaments.
TROPONIN
 Each actin molecule is called F-actin and it is the
 Troponin is bound very tightly to tropomyosin and moves tropomyosin
polymer of a small protein known as G-actin.
away from myosin-binding sites during muscle contraction.
 The actin molecules in the actin filament are also
OTHER PROTEINS OF THE MUSCLE
arranged in the form of a double helix.
In addition to the contractile proteins, the sarcomere contains several other
 F-actin molecule has an active site to which the myosin
proteins such as:
head is attached
1. Actinin, which attaches actin filament to ‘Z’ line.
2. Desmin, which binds ‘Z’ line with sarcolemma.
3. Nebulin, which runs in close association with and parallel to actin
filaments.
4. Titin, a large protein connecting ‘M’ line and ‘Z’ line.
Each titin molecule forms scaffolding (framework) for sarcomere and provides
elasticity to the muscle. 15
 CONCENTRIC AND ECCENTRIC CONTRACTION

 A concentric contraction is a type of muscle contraction in

 Tension is generated by the muscle as cross-bridges are
which the muscles shorten while generating force.
reformed.
 The muscle fiber will shorten (contract) if a sufficient
 For the muscle as a whole to contract, the actin and myosin
number of sarcomeres actively shorten and if either one or
filaments must overlap, causing the sarcomere to shorten.
both ends of the muscle fiber are free.
 This process is triggered by the release of calcium ions in the
 In Shortening/concentric contraction, thin filaments are
presence of troponin and tropomyosin.
being pulled toward the thick filaments.
 The release of calcium, which is provided by ATP, facilitates the
 Eccentric contraction, also known as lengthening
interaction of myosin and actin at the molecular level.
contraction.

 In a lengthening/eccentric contraction, the thin filaments are

pulled away from the thick filaments, and cross-bridges are

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broken and reformed as the muscle lengthens.
 Mechanism of
Muscle
Contraction
David T. OLUWOLE
Department of Physiology
College of Health Sciences, CUAB
 Mechanism of Excitation
 When the alpha motoneuron creates an action potential, it will reach the neuromuscular junction.

 The neuromuscular junction will form a new action potential on the motor endplate.

 This action potential will spread along the sarcolemma of the skeletal muscle cell and into the T-tubules.

 The action potential will activate the dihydropyridine receptors in the T-tubules, which will open the ryanodine receptors, allowing

Ca2+ to flow out from the sarcoplasmic reticulum and into the sarcoplasm.

Mechanism of Contraction
 During rest, when there is no contraction, the protein tropomyosin prevents actin and myosin from interacting with each other, thereby

preventing contraction.

 Before contraction, the myosin heads hydrolyse one ATP into ADP and inorganic phosphate. This hydrolysis puts the head in a high-

energy state: we say that the head is now “cocked”.

 After excitation, the intracellular level of Ca2+ is increased. Ca2+ binds to the protein troponin on the thin filaments. This moves

tropomyosin out of the way. The so-called cross-bridge cycle begins.

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NEUROMUSCULAR JUNCTION

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 Neuromuscular Transmission
 Action Potentials arriving at the presynaptic terminal cause
Voltage-gated Ca2+ channels to open
 Ca2+ uptake into the terminal causes release of the neurotransmitter
acetylcholine into the synaptic cleft (The ACH is already
synthesized and stored in synaptic cleft)

 ACH diffuses across the synaptic cleft and binds to its receptors on
the sarcolemma

 This causes opening of ion channels in the receptors allowing the

simultaneous passage of Na+ into the muscle fibre and K+ out

of the muscle fibre.

 More Na+ ions enters than K+ ions thus causing another

membrane potential called END PLATE POTENTIAL

 The ACH effects are terminated by its breakdown in the

synaptic cleft by acetylcholinesterase.
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 Excitation and Contraction in Summary

 During rest, when there is no contraction, the protein tropomyosin prevents actin and myosin from interacting with each other, thereby
preventing contraction.
 Before contraction, the myosin heads hydrolyse one ATP into ADP and inorganic phosphate. This hydrolysis puts the head in a high-
energy state: we say that the head is now “cocked”.

 After excitation, the intracellular level of Ca2+ is increased. Ca2+ binds to the protein troponin on the thin filaments. This moves
tropomyosin out of the way. The so-called cross-bridge cycle begins.

1. Now that there is nothing to prevent acting and myosin from interacting, the myosin head will immediately bind to actin
2. This binding causes a conformational change in the myosin head, which causes the head to move toward the M-line, pulling the thin
filament with it. This is called the power stroke. The energy for this comes from the ATP which was hydrolysed before the cycle
started. After the power stroke the head is now “uncocked”
3. After the power stroke, another molecule of ATP binds to myosin. This causes the myosin head to be released from actin
4. The ATP molecule is hydrolysed into ADP and Pi, resetting the head into the “cocked” position
5. The myosin head binds to actin in the thin filament again, but this time at a different site
The cross-bridge cycle repeats as long as the intracellular Ca2+ level remains increased and there is ATP available. Approx. 10 – 100 cycles
occur per second.
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 Excitation
and
Contraction
of the
skeletal
Muscle

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 Excitation
and
Contraction
of the
skeletal
Muscle

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 Myosin releases
from Actin
Excitation filament: Myosin
If Ca2+ is < head returns to
and 𝟏 𝝁𝒎𝒐𝒍 𝒅𝒎−𝟑 , starting position
contraction
Contraction ends
of the
skeletal
Stimulus Ca2+ regulation Without ATP, myosin
ATP Present,
Muscle ATP binds to heads remain bound to
myosin actin filaments: rigor
mortis ensues

If Ca2+ is ≥
𝟏 𝝁𝒎𝒐𝒍 𝒅𝒎−𝟑 ,
new
contraction
cycle begins

Myosin head Further distortion of myosin

binds to Actin head with release of ADP

ATP Hydrolysis Myosin head turn

as Pi released

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Contraction and Relaxation Principle between Actin and Myosin Filaments

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The cross-bridge cycle

(d)

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 Properties of Skeletal Muscles
 Excitability: it is ability of muscle fiber to respond to different types of stimulus (that
change in environment) around and it is a physicochemical change.
 Stretchibility: muscle fiber gets stretched before contraction.
 Elasticity: It is the ability of the muscles to return to its original structure when released.
 Contractility: Ability to Shorten when adequate stimulus is received

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 Muscle Fibres Types
There are two types of muscle fibres present in birds and mammals: Red muscle fibre and White muscle fibre

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 Electrical Changes during Muscular Contraction
 Electrical events occur in the muscle during resting condition as well as active conditions.
 Electrical potential Changes during Muscular Contraction in the muscle during resting condition is called
RESTING MEMBRANE POTENTIAL.
 Electrical changes that occur in active conditions, i.e. when the muscle is stimulated are together called
ACTION POTENTIAL.
Resting Membrane Potential

 Resting membrane potential is defined as the electrical potential difference (voltage) across the cell membrane (between
inside and outside of the cell) under resting condition
 The condition of the muscle during resting membrane potential is called polarized state.
 In human skeletal muscle, the resting membrane potential is –90 mV.
 Development and maintenance of resting membrane potential in a muscle fiber or a neuron are carried out by movement
of ions, which produce ionic imbalance across the cell membrane and is dependent on:
1. Activities Sodium-potassium pump
2. Selective permeability of cell membrane. 30
 Electrical Changes during Muscular Contraction
Action Potential

 Action potential is defined as a series

of electrical changes that occur in the

membrane potential when the muscle

or nerve is stimulated.

 Action potential occurs in two phases:

1. Depolarization; 2. Repolarization.

 The 3 major parts of Action potential:

1. Latent period 2. Depolarization 3.

Repolarization.

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 Chemical Changes during Muscular Contraction
 Muscle contraction requires energy;
 muscle is the machine for converting chemical energy into mechanical work.
 The energy necessary for muscular contraction is liberated during the processes of breakdown and resynthesis of ATP.
Breakdown of ATP
Resynthesis of ATP
 ATP is broken into ADP and inorganic phosphate (Pi) and
energy is liberated. Energy liberated by breakdown of ATP
 ADP formed during ATP breakdown, is immediately
is responsible for:
utilized for the resynthesis of ATP.
1. Spread of action potential into the muscle
 But for this resynthesis process, ADP cannot combine
2. Liberation of calcium ions from cisternae of ‘L’ tubules
with Pi, rather It combines with a high-energy phosphate
into the sarcoplasm
radical
3. Movements of myosin head
The sources for this high-energy phosphate can only be:
4. Sliding mechanism
1. creatine phosphate (phosphorylcreatine);
 Energy liberated during ATP breakdown is sufficient for
2. carbohydrate metabolism
maintaining full contraction of the muscle for a short
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duration of less than one second
 Clinical Correlates
Rigor
 Rigor refers to shortening and stiffening of muscle fibers It can be:  Meanwhile, the muscle needs to drive out the calcium;
 Heat rigor: the rigor that occurs due to increased temperature,  However, this requires ATP. During death processe, the ATP
(irreversible) Caused by coagulation of muscle proteins, actin and molecules are completely exhausted.
myosin.  Hence the rigidity remain until the onset of decomposition since the
1) Cold rigor: Due to the exposure to severe cold, (reversible) muscles remain in contracted state.
2) Calcium rigor: Due to increased calcium content, (reversible)
 Clinically, Rigor mortis is useful in determining the time of death.
3) Rigor mortis: Develops after death.
Myasthenia Gravis
Rigor mortis
 An autoimmune disease of neuromuscular junction caused by
 A condition of the body after death, characterized by stiffness
antibodies to cholinergic receptors
of muscles and joints, occurs due to stoppage of aerobic
 It is characterized by grave weakness of the muscle due to the
respiration, causing changes in the muscles.
inability of neuromuscular junction to transmit impulses from
 Soon after death, the cell membrane becomes highly permeable
nerve to the muscle
to Ca2+, large Ca2+ enters the muscle fibers
 It is an autoimmune disease in which the body develops
 This promotes formation of actomyosin complex resulting in
antibodies against its own acetylcholine receptors.
contraction muscles.
 The antibodies prevent binding of acetylcholine with it
 Few hours after death, the muscles of body undergo severe
receptors or destroy the receptors
contraction and become rigid with the joints becoming stiff and
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locked.
QUESTIONS

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