MUSCLES

CHAPTER OUTLINE
• Types of muscles in the human body
• Motor unit of skeletal muscles
• Sliding filament theory of contraction
• Role of calcium in muscle contraction
• Excitation-contraction coupling
• Energy requirements and metabolism of skeletal muscles
• Oxygen debt
• Muscle fatigue
Classification of Muscles Striated
muscle
Muscles are classified by Striations
Non-striated
three different methods muscle

Voluntary
muscle
Muscles Control
Classification Involuntary
muscle

Skeletal
muscle

Cardiac
Situation
muscle

Smooth
muscle
 STRUCTURE OF SKELETAL MUSCLE
 The human body has more than 600 skeletal muscles
 Muscle mass comprises a large number of individual muscle cells or myocytes.
 Skeletal muscle fibers are multinucleated and are arranged parallel to one another with
some connective tissue in between.
 Muscle mass is separated from the neighboring tissues by a thick fibrous tissue layer
known as fascia.
 Beneath the fascia, the muscle is covered by a connective tissue sheath called epimysium.
 The muscle fibers are arranged in various groups called bundles or fasciculi.
 The connective tissue sheath that covers each fasciculus is called perimysium.
 Each muscle fiber is covered by a connective tissue layer called the endomysium
 The Tendon of some muscles is thin, flat, and stretched but tough, called as
aponeurosis
Aponeurosis
 MUSCLE FIBERS (MYOCYTE)
 Skeletal muscles are composed of numerous muscle cells also called as muscle fibers
ranging from 10 to 80 micrometers in diameter and usually innervated by only one
nerve ending.

 The Sarcolemma Is a Thin Membrane Enclosing a Skeletal Muscle Fiber, made up of

polysaccharide material that contains numerous thin collagen fibrils.

 Myofibrils Are Composed of interdigitated Actin (3000) and Myosin (1500)

Filaments.

 Sarcoplasm Is the Intracellular Fluid Between Myofibrils, also contains mitochondria

that lie parallel to the myofibrils.


MUSCLE FIBER (MYOCYTE)

ORGANELLES OF MUSCLE
FIBER
 Nuclei.
 Myofibril.
 Golgi Apparatus.
 Mitochondria.
 Sarcoplasmic Reticulum.
 Ribosomes.
 Glycogen Droplets.
 Occasional lipid droplets.
 MYOFIBRIL
 Myofibrils or Myofibrillae are the fine parallel filaments present in sarcoplasm of the
muscle cell.
 The diameter of the myofibril is 0.2 to 2 μ and the length varies between 1 cm and 4cm.
 Each myofibril consists of a number of two alternating bands which are also called
sections, segments, or disks. These bands are formed by muscle proteins.

The two bands are:

1. Light band or ‘I’ band.
2. Dark band or ‘A’ band.
 MYOFIBRIL BANDS
Light Band or ‘I’ Band
 Light band is called ‘I’ (isotropic) band
because it is isotropic to polarized light.

Dark Band or ‘A’ Band

 Dark band is called ‘A’ (anisotropic) band
because it is anisotropic to polarized light
 Dark band is also called ‘Q’ disk

 I band is divided into two portions, by means

of a narrow and dark line called ‘Z’ line or ‘Z’
disk.
Organization of skeletal muscle, from the gross to the molecular level
 SARCOMERE – CONTRACTILE
UNIT OF THE MUSCLE

Each Titin molecule extends from the Z disk to the M line. Part of the titin molecule is closely associated with the
myosin thick filament, whereas the rest of the molecule is springy and changes length as the sarcomere contracts and
relaxes.
 SARCOMERE
 Sarcomere (basic contractile unit) is defined as the structural and functional unit of a
skeletal muscle (2μm), extends between two ‘Z’ lines of myofibril.
 In the middle of ‘A’ band, there is a light area called ‘H’ zone.
 In the middle of ‘H’ zone lies the middle part of myosin filament. This is called ‘M’ line
 Sarcomere consists of many thread like structures called myofilaments.

Myofilaments are of two types:

1. Actin filaments (thin filaments)
2. Myosin filaments. (thick filaments)
 MYOFILAMENTS
ACTIN FILAMENTS
Actin filaments are composed of following molecules
1. F-actin or actin molecules
2. Tropomyosin
3. Troponin
F-ACTIN OR ACTIN MOLECULES
 F-actin or actin molecules is the major constituents of the thin actin filaments.
 Each F-actin and it is the polymer of a small protein known as G-actin.
 Attached to each one of the G-actin molecules is one molecule of ADP.
 These ADP molecules are believed to be the active sites on the actin filaments
with which the cross-bridges of the myosin filaments interact to cause muscle
contraction.
TROPOMYOSIN
 About 40 to 60 tropomyosin molecules are situated along the double helix strand of actin filament.
 In the resting state, the tropomyosin molecules lie on top of the active sites of the actin strands so that
attraction cannot occur.
TROPONIN
It is formed by three subunits:
1. Troponin I, which is attached to F-actin
2. Troponin T, which is attached to tropomyosin
3. Troponin C, which is attached to calcium ions
 One of the subunits (troponin I) has a strong affinity for actin, another (troponin T) for tropomyosin, and a
third (troponin C) for ca++ ions.
MYOSIN OR THICK FILAMENT
• Each myosin filament is composed of 200 or more individual myosin molecules.
• Each myosin molecule has two portions:
1. Tail portion
2. Head portion
 The myosin molecule is composed of six polypeptide chains—two heavy chains,
each with a molecular weight of about 200,000; and four light chains, with
molecular weights of about 20,000 each.
 The two heavy chains wrap spirally around each other to form double helix, which is
called the tail of the myosin molecule.
 One end of each of these chains is folded bilaterally into a globular polypeptide
structure called a myosin head (two free heads). The four light chains are also part
of the myosin head.
 The protruding arms and heads together are called cross-bridges, Each cross-bridge
is flexible at two points called hinges.
 ADENOSINE TRIPHOSPHATASE
ACTIVITY OF THE MYOSIN HEAD
 Myosin head functions as an adenosine triphosphatase (ATPase) enzyme.
 This property allows the head to cleave ATP and use the energy derived from the
ATP’s high-energy phosphate bond to energize the contraction process.
 SARCOTUBULAR SYSTEM
(EXCITATION-CONTRACTION COUPLING)
 It is a system of membranous structures in the form of vesicles and tubules in the
sarcoplasm of the muscle fiber.
 It surrounds the myofibrils embedded in the sarcoplasm
 Sarcotubular system is formed mainly by two types of structures.
1. T-tubules
2. L-tubules or sarcoplasmic reticulum.
 The L-tubules dilate to form a pair of lateral sacs called terminal cisternae, which is in
close contact with T-tubule.
 The T-tubule along with the cisternae on either side is called the triad of skeletal muscle.
Transverse (T) tubule–sarcoplasmic reticulum system. Note
that the T tubules communicate with the outside of the cell
membrane and, deep in the muscle fiber, each T tubule lies
adjacent to the ends of longitudinal sarcoplasmic reticulum
tubules that surround all sides of the actual myofibrils that
contract. This illustration was drawn from frog muscle,
which has one T tubule per sarcomere, located at the Z disk.
A similar arrangement is found in mammalian heart muscle,
but mammalian skeletal muscle has two T tubules per
sarcomere, located at the A-I band junctions.
 FUNCTIONS OF SARCOTUBULAR
SYSTEM
T-tubules:
 Rapid transmission of impulse in the form of action potential from the sarcolemma to
the myofibrils.

L-tubules:
 Store a large quantity of ca++ ions.
 When an action potential reaches the cisternae of the L-tubule, the calcium ions are
released into the sarcoplasm.
 Calcium ions trigger the processes involved in the contraction of the muscle,
excitation-contraction coupling.
CONTRACTION AND RELAXATION
OF MUSCLE
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 of the muscle.

During the relaxation

Relaxed and contracted states of a myofibril showing (top) sliding of the
 The actin filaments and ‘Z’ lines come back to actin filaments (pink) into the spaces between the myosin filaments
(red) and (bottom) pulling of the Z membranes toward each other.

the original position.

 MOLECULAR BASIS OF MUSCULAR
CONTRACTION

Molecular mechanism is responsible for formation of actomyosin complex

that results in muscular contraction.

It includes three stages:

1. Excitation-contraction coupling.
2. Role of troponin and tropomyosin.
3. Sliding mechanism.
EXCITATION-
CONTRACTION
COUPLING
Excitation-contraction coupling in skeletal
muscle. The top panel shows an action
potential in the transverse tubule that
causes a conformational change in the
voltage-sensing dihydropyridine (DHP)
receptors, opening the ryanodine (RyR)
Ca2+ release channels in the terminal
cisternae of the sarcoplasmic reticulum
and permitting Ca2+ to diffuse rapidly
into the sarcoplasm and initiate muscle
contraction.
During repolarization (bottom panel), the
conformational change in the DHP
receptor closes the Ca2+ release channels,
and Ca2+ is transported from the
sarcoplasm into the sarcoplasmic
reticulum by an adenosine triphosphate–
dependent calcium pump, called SERCA
(sarcoplasmic reticulum Ca2+-ATPase)
Excitation-contraction coupling in the muscle, showing
(1) an action potential that causes release of calcium ions from the sarcoplasmic reticulum and then
(2) re-uptake of the calcium ions by a calcium pump. ATP, Adenosine triphosphate.
 ROLE OF TROPONIN AND
TROPOMYOSIN
 The head of myosin molecules has a strong tendency
to get attached with active site of F actin.
 In relaxed condition, the active site of F actin is
covered by the tropomyosin.
 Ca++ binds with troponin C and produces changes.
 Pulls tropomyosin molecule away from F actin.
 The active site of F actin is uncovered and exposed.
 The head of the myosin gets attached to the actin.
SLIDING MECHANISM OF
MUSCLE CONTRACTION
(SLIDING THEORY)
SLIDING MECHANISM AND
F O R M AT I O N O F
ACTOMYOSIN COMPLEX –
S L I D I N G T H E O RY
R AT C H E T T H E O R Y O R WA L K
A L O N G T H E O R Y.
Sequence of events during
muscular relaxation
TYPES OF MUSCLE CONTRACTIONS
Contraction is defined as the internal events of muscle with change in either length
or tension of the muscle fibers.

 Muscular contraction is classified into two types

1.Isotonic contraction
 Muscular contraction in which the tension remains the same and the length of the
muscle fiber is altered. i.e. Simple flexion of arm.
 Types: Concentric, Eccentric.
2.Isometric contraction
 Muscular contraction in which the length of muscle fibers remains the same and the
tension is increased. i.e. Pulling any heavy object.
Isotonic and isometric systems for recording muscle
contractions.
Isotonic contraction occurs when the force of the muscle
contraction is greater than the load, and the tension on the muscle
remains constant during the contraction. When the muscle
contracts, it shortens and moves the load.
Isometric contraction occurs when the load is greater than the
force of the muscle contraction; the muscle creates tension when it
contracts, but the overall length of the muscle does not change.
A motor unit consists of a motor neuron and
the group of skeletal muscle fibers it innervates.
A single motor axon may branch to innervate
several muscle fibers that function together as a
group. Although each muscle fiber is innervated
by a single motor neuron, an entire muscle may
receive input from hundreds of different motor
neurons.
NEUROMUSCULAR JUNCTION

• Neuromuscular junction is the junction/synapse between the axon

terminal of the nerve fiber and muscle fiber.
STRUCTURE OF NEUROMUSCULAR JUNCTION

Different views of the motor end plate.

A, Longitudinal section through the end plate.
B, Surface view of the end plate.
C, Electron micrographic appearance of the contact point between a single axon terminal and the muscle fiber membrane.
 NEUROMUSCULAR JUNCTION
 Each terminal branch innervates one muscle fiber through the
neuromuscular junction.
 When the axon comes close to muscle fiber, it loses the myelin sheath and
contains mitochondria and neurotransmitters.
 The axis cylinder is exposed. This portion of the axis cylinder is expanded
like a bulb, which is called a motor endplate.
 The motor endplate invaginates inside the muscle fiber and forms a
depression, which is known as synaptic trough or synaptic gutter.
NEUROMUSCULAR JUNCTION
 Membrane of the nerve ending is called the presynaptic membrane.
Membrane of the muscle fiber is called postsynaptic membrane. Space
between these two membranes is called synaptic cleft.
 Synaptic cleft contains basal lamina. It is a thin layer of spongy reticular
matrix through which, the extracellular fluid diffuses.
 An enzyme called acetylcholinesterase (AchE) is attached to the matrix of
basal lamina, in large quantities.
 Postsynaptic membrane is the membrane of the muscle fiber. It is thrown into
numerous folds called subneural clefts.
 Postsynaptic membrane contains the receptors called nicotinic acetylcholine
receptors
Events of Neuromuscular Transmission
A series of events take place in the neuromuscular junction during this process.

The events are:

1. Release of acetylcholine
2. Action of acetylcholine on its receptors
3. Development of miniature endplate potential
4. Development of endplate potential
5. Generation of action potential
6. Destruction of acetylcholine.
Release of acetylcholine from synaptic vesicles at the neural
membrane of the neuromuscular junction.

Note the proximity of the release sites in the neural membrane

to the acetylcholine receptors in the muscle membrane at the
mouths of the subneural clefts.
Acetylcholine-gated channel.
A: Closed state.
B: After acetylcholine (Ach) has become attached and a
conformational change has opened the channel, allowing
sodium ions to enter the muscle fiber and excite
contraction. Note the negative charges at the channel
mouth that prevent passage of negative ions such as
chloride ions.
SKELETAL MUSCLE ACTION POTENTIAL
• RMP = -90 mV
• Duration = 1-5 ms
• Conduction velocity
= 3-5 m/sec
 DRUGS ACTING ON
NEUROMUSCULAR JUNCTION
 NEUROMUSCULAR BLOCKERS
Neuromuscular blockers are the drugs, which
prevent transmission of impulses from nerve fiber
to the muscle fiber through the neuromuscular
junctions.

1. Curare
2. Bungarotoxin (Toxin from venom of deadly
snake)
3. Succinylcholine and Carbamylcholine
4. Botulinum Toxin (prevents release of Ach
from nerve terminal)
 DRUGS STIMULATING
NEUROMUSCULAR JUNCTION

Neuromuscular junction can be

stimulated by some drugs like
 Neostigmine
 Physostigmine
 Diisopropylfluorophosphate.
These drugs inactivate the enzyme,
acetyl cholinesterase
DISORDERS OF NEUROMUSCULAR
JUNCTION
MYASTHENIA GRAVIS
 Myasthenia gravis is an autoimmune disorder of neuromuscular junction caused
by antibodies to cholinergic receptors.

EATON-LAMBERT SYNDROME
 Eaton-Lambert syndrome is also an autoimmune disorder of neuromuscular
junction.
 It is caused by antibodies to calcium channels in axon terminal.
 MYASTHENIA GRAVIS
 Myasthenia gravis is an autoimmune disease of neuromuscular junction caused by
antibodies to cholinergic receptors. is treated by cholinesterase inhibitors i.e.
neostigmine pyridostigmine.
 It is characterized by grave weakness of the muscle due to the inability of
neuromuscular junction to transmit impulses from nerve to the muscle.
Symptoms
 Slow and weak muscular contraction
 Inability to maintain the prolonged contraction
 Quick fatigability
 Double vision and droopy eyelids
 Difficulty in swallowing and speech
 ENERGY REQUIRED FOR
MUSCULAR CONTRACTION
Muscles need energy for the following events during contraction:

• Walk-along mechanism (formation of actomyosin complex and power stroke)

• Working of Ca++ pump
• Restoration of Na+ and K+ gradient (RMP)
SOURCES OF ENERGY FOR MUSCLE
CONTRACTION
• Free ATP (2 sec) Phosphagen system
• Phosphocreatine (5 – 8 sec)
The first source of energy that is used to reconstitute the ATP is the substance phosphocreatine, which
carries a high-energy phosphate bond similar to the bonds of ATP.
• Glycolysis- anaerobic respiration (2 min)
The second source of energy, which is used to reconstitute both ATP and phosphocreatine, is a process called
glycolysis—the breakdown of glycogen previously stored in the muscle cells. Rapid enzymatic breakdown of
the glycogen to pyruvic acid and lactic acid liberates energy that is used to convert ADP to ATP.
• Oxidative metabolism (95%)
The third source of energy is oxidative metabolism, which means combining oxygen with the end products of
glycolysis and with various other cellular foodstuffs to liberate ATP. More than 95% of all energy used by the
muscles for sustained long-term contraction is derived from oxidative metabolism.
DURATION OF ENERGY PROVIDED BY
EACH SOURCE
• Phosphagen system: 8-10 seconds
• Glycogen–lactic acid system: 1.3-1.6 minutes
• Aerobic system Unlimited time: (as long as nutrients last)
 RESYNTHESIS OF ATP
Resynthesis of ATP from creatine phosphate
 The reaction is called Lohmann’s reaction (CrP-ATP system).
ADP + CP → ATP + Creatine

Resynthesis of ATP by carbohydrate metabolism

 Catabolic reactions of glycogen in the muscle (stored in
sarcoplasm)
 It is called glycolytic pathway or Embden-Meyerhof pathway
Glycolysis/EmbdenMeyerhof pathway
Number of ATP molecules formed in this pathway:
Total ATP formed = 4 molecules
Loss of ATP during phosphorylation = 2 molecules
Net ATP formed during glycolysis = 2 molecules
 C O R I C Y C L E ( A N E R O B I C G LY C O LY S I S )
KREBS CYCLE, (TCA CYCLE) OR CITRIC ACID CYCLE (AEROBIC
G LY C O LY S I S )
SUMMARY OF RESYNTHESIS OF ATP DURING
CARBOHYDRATE METABOLISM

A total of 38 ATP molecules are formed during breakdown of each

glycogen molecule in the muscle.
OXYGEN DEBT
• The difference between the amount of oxygen needed by the muscles and the
actual amount present is called the oxygen debt.
• Heavy exercise causes the development of Oxygen Debt due to the following
reasons
1. Depletion of oxygen stores in the body
The oxygen normally present in the body is 2 L
• 0.5 L in the air of the lungs
• 0.25 L in body fluids
• 1 L combined with the hemoglobin of the blood, and
• 0.3 liter stored in the muscle fibers, combined mainly with myoglobin
Almost all this stored oxygen is used within a minute or so for aerobic metabolism.
2. Depletion of ATP and creatine phosphate in muscles
3. Accumulation of Lactic acid.
REPAYING THE OXYGEN DEBT
• After a hard exercise, extra consumption of oxygen by breathing hard and consuming large
amounts of oxygen for at least a few minutes and sometimes for as long as 1 hour thereafter
repays the oxygen debt.
• This additional oxygen is used to
1. reconvert the lactic acid that has accumulated during exercise back into glucose,
2. reconvert adenosine monophosphate and ADP to ATP,
3. reconvert creatine and phosphate to phosphocreatine,
4. re-establish normal concentrations of oxygen bound with hemoglobin and myoglobin,
and (5) raise the concentration of oxygen in the lungs to its normal level.
• This extra consumption of oxygen after exercise is called repaying the oxygen debt.
REPAYING OF OXYGEN DEBT
• During exercise (First 4 min): rat of oxygen uptake > 15-fold.
• After the exercise is over, the oxygen uptake still
remains above normal; at first it is very high while the
body is reconstituting the phosphagen system and
repaying the stored oxygen portion of the oxygen debt,
and then it is still above normal although at a lower
level for another 40 minutes while the lactic acid is
removed. The early portion of the oxygen debt is called
• the alactacid oxygen debt and amounts to about 3.5
liters.
• The latter portion is called the lactic acid oxygen debt
and amounts to about 8 liters.
 MUSCLE FATIGUE
• Muscle fatigue is the progressive
weakness and loss of contractility that
results from prolonged use of the
muscles.
• Fatigue has multiple causes:

• ATP synthesis declines due to

depleted glycogen stores.
• Accumulation of lactic acid.
• Motor nerve fibers use up their
acetylcholine (junctional fatigue).
• Interruption of blood flow
WHERE TO STUDY FROM?
• Essentials of Medical Physiology By Jaypee publishers
Chapters 26, 27, 29, 30

• Guyton and Hall, Textbook of Medical Physiology

Chapters 73-85 for Oxygen debt
Chapter 6 for muscle fatigue