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MUSCLE PHYSIOLOGY
10 marks
1. NEUROMUSCULAR JUNCTION
Neuro Muscular Junction is the junction between a motor nerve ending and a
muscle fiber
Physiologic Anatomy
- Terminal buttons – Divisions at the end of motor neuron
- Synaptic gutter - the depression on the skeletal muscle fiber
- Motor end plate - the thickened part of the sarcolemma
- Junctional folds - folds of motor end plate
- Presynaptic membrane – membrane of the nerve terminal
- Postsynaptic membrane - muscle membrane
- Synaptic cleft - The space between the two membranes
- Synaptic vesicles – Vesicles containing the neurotransmitter Acetyl choline
at presynaptic nerve terminal
- Ach receptors – Receptors found on the post synaptic membrane

Synaptic gutter

Motor End plate

Events in transmission

Arrival of nerve impulse at the presynaptic nerve terminal

↓
Depolarisation of the presynaptic nerve terminal
↓
Opening up of the Ca++ channel and entry of calcium into the presynaptic membrane
↓
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Release of the neurotransmitter (Ach) from vesicles into the synaptic cleft
↓
Fusion of the synaptic vesicle with the presynaptic membrane
↓
Rupture of vesicles & release of Ach into the synaptic cleft
↓
Binding of the Ach with the receptors on the post synaptic membrane
↓
Permeability of post synaptic membrane to Na+ increases
↓
Depolarisation of the post synaptic membrane-generation of End Plate Potential
↓
End Plate Potential reaches threshold & an action potential is produced which is
propagated.
DRUGS ACTING ON NMJ
1. Neuro Muscular Blockers
a) Botulinum toxin –
A bacterial toxin which inhibits the synthesis or release of Ach
b) Tubocurarine
By competitive inhibition.
c)  Bungarotoxin
By irreversible combination with the receptor
2. Drugs that stimulate Transmission
a) Neostigmine, Physostigmine
By inactivating Anticholinesterase → Prolonged depolarisation
Used in treating Myasthenia gravis
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2.EXCITATION-CONTRACTION COUPLING

DEFINITION:
The process in which depolarization of the muscle fiber initiates its
contraction is called excitation-contraction coupling.
i.e electrical phenomenon is converted in to mechanical phenomenon.
Nerve Action Potential
↓ Neuromuscular transmission
Muscle Action Potential
↓ Excitation contraction coupling
Muscular contraction
EVENTS

• Release of Acetylcholine from nerve terminal

• Binding of acetylcholine to the receptors present on the motor end plate
• Increased Na+ and K+ conductance in end- plate membrane
• Generation of end plate potential
• When the end plate potential reaches the firing level → generation of action
potential in muscle fibers.
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• Spread of depolarization along T tubules to interior of the muscle fiber

• Change in configuration of DHP receptors in membrane of “T” tubule → opens
ryanodine receptors (Ca2+ channels) of cisternae→ release of calcium into the
cytosol
• Ca2+ diffuses to thick and thin filaments.
• Thin actin filaments slide over the thick myosin filaments
• Z lines come closure → Shortening of sarcomere →Muscle contraction

Action potential

Motor end plate

Cisternae

3. MOLECULAR MECHANISM OF MUSCULAR

CONTRACTION/ SLIDING FILAMENT THEORY
EVENTS DURING MUSCULAR CONTRACTION
• Electrical events
• Mechanical events
• Chemical events
• Thermal events
ELECTRICAL EVENTS
• Transmission of nerve impulse to muscle across NMJ
• Excitation of muscle → development of muscle action potential
• Transmission of muscle action potential through “T” tubules to interior of muscle fiber
• release of calcium into the cytosol
MECHANICAL OR MOLECULAR EVENTS
• Explained by sliding filament theory-proposed by Huxley and Huxley in
1969. Most accepted theory
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• States that muscular contraction is due to sliding of actin filaments over the
myosin filaments.
• Involves two important sequences:
• Exposure of myosin binding sites of actin molecules
• Cross bridge cycle
Exposure of myosin binding sites of actin molecules
• Binding of calcium to troponin C
• Conformational change of troponin C.
• Lateral movement of tropomyosin – troponin complex from actin filaments
• Exposure of myosin binding sites of actin molecules
Cross bridge cycle
1. Activation of myosin ATPase enzyme
2. Hydrolysis of an ATP molecule → release of energy → activation of myosin crossbridges
3. Binding of crossbridges to the actin filaments
4. Bending of myosin head when ADP and P are released from the crossbridges → pulls the
actin filament towards the centre of sarcomere (powerstroke)
5. Binding of another ATP molecule → detachment of crossbridges from actin filaments
6. Binding of another ATP molecule → Attachment of crossbridge to another distal actin
molecule
CROSSBRIDGE CYCLE
Attachment – Swivel (power stroke) – detachment – attachment again.
RELAXATION OF MUSCLE
• reuptake of Ca2+ into sarcoplasmic reticulum (SR)
• Troponin-tropomyosin move back to their position and cover the active sites of actin
filaments.
▪ Interaction between the actin & myosin ceases
▪ The muscle relaxes

CHEMICAL EVENTS
• Energy is provided by hydrolysis of ATP & creatine phosphate
Contraction-Relaxation Steps Requiring ATP
• For binding of myosin crossbridges to actin filaments
• Detachment of crossbridges from actin filaments
• Active transport (Pumping) of Ca2+ back into sarcoplasmic reticulum

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5 & 3 marks

1.SARCOMERE
• Sarcomere is the contractile unit of the muscle fiber.
• It is the distance between two “Z” lines.
• It consists of “A” band at the center and half of the “I” band at the sides.
• “A” band is made up of thick myosin filaments and “I” band is made up of thin
actin filaments.
The length of sarcomere at rest is about 2.5 µm. During muscle contraction the length of
sarcomere reduces to 1.5 µm. During stretching it increases in length to 3.5µm.
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2. MOTOR UNIT
Definition: A single motor neuron with all its axonic terminals and the muscle fibers
supplied by it
Size principle:
The size of the type I motor unit is larger i.e., the number of muscle fibers supplied
by a single motor neuron is high. Type I motor unit controls the gross movements & the
muscle fibers involved are slow red muscle fibers.
The size of the type II motor unit is smaller i.e., the number of muscle fibers
supplied by a single motor neuron is low. Type II motor unit controls the fine skilled
movements & the muscle fibers involved are fast white muscle fibers.

3.SMOOTH MUSCLE CONTRACTION/ ROLE OF CALMODULIN

Steps involved:

1. Depolarisation of smooth muscle fibers

2. Release of calcium from sarcoplasmic reticulum
3. Calcium bind to “Calmodulin”(calcium binding protein in smooth
muscle fibers)
4. This calcium- calmodulin complex activates myosin light chain
kinase
5. The enzyme light chain kinase causes phosphorylation of myosin
6. Sliding of actin over myosin
4. SMOOTH MUSCLE PROPERTIES
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APPLIED
MUSCLE PHYSIOLOGY Applied
1. What is the physiological basis of administration of Neostigmine to a patient with
myasthenia gravis?
Neostigmine inhibits the action of acetylcholine esterase enzyme → prolonged depolarization
→ increase in the degree of contraction
2. Name the drugs that interfere with neuro-muscular transmission
Drugs that block Transmission
Botulinum toxin – a bacterial toxin, Tubocurarine, Suxamethonium &  Bungarotoxin
Drugs that stimulate Transmission
• Neostigmine & Physostigmine
3. Explain the basis of the use of curare form of drugs as muscle relaxants and the
use of anticholinestrases in treatment of myasthenia gravis
- Curare form of drugs block the neuromuscular transmission by competitive inhibition
- Anticholinestrases inhibit the action of acetylcholine esterase enzyme
4. What is rigors mortis? What is its clinical significance?
Rigidity after death is called rigor mortis. Clinical significance – to find out the time
of death
5. A man after prolonged illness died. Several hours after death, his body becomes
rigid.
What is that phenomenon called?
Why rigidity occurs after death?
i) Rigor mortis
ii) Unavailability of ATP . The non availability of ATP after the muscle had started to
shorten will not allow the muscle to relax. So the muscle will remain rigid.
6. Explain the medicolegal importance of “Rigor Mortis”
Rigor mortis is development of rigidity of body after death. Rigidity develops 4-5
hours after death and disappears within 24 hours. This is useful in finding out the time of
death
7. Explain the pathophysiology of myasthenia gravis
Myasthenia gravis is an autoimmune disorder characterized by inability of
neuromuscular junction to transmit signals from nerve fiber to muscle
Cause: Antibodies against acetylcholine receptors on motor end plate
Features:
- Paralysis of skeletal muscles
- Muscle strength is greatest in the morning and least in the evening
- EMG recorded on continuous effort shows a gradual decline in the
amplitude of potentials
Treatment:
a) Neostigmine & Physostigmine (anticholinesterase) – destroys acetylcholine
esterase & potentiates the effect of acetylcholine on the end plate
b) Steriods – destroy lymphocytes & there by reduce the antibody titre
11. A female patient of 40 yrs. age complains of drooping of eye lid and general
weakness and fatigue that aggravates towards evening, but improves after
rest or sleep. What could be your provisional diagnosis and what is the
nature of dysfunction? Give the physiological basis of use of a drug in this
condition.
Diagnosis : Myasthenia gravis .
Drug: Neostigmine (anticholinesterase) – destroys acetylcholine esterase &
potentiates the effect of acetylcholine on the end plate