Note: Dr. Prema Sembulingam's Essentials of Medical Physiology is not in the textbook library. The answer below is drawn from Guyton and Hall Textbook of Medical Physiology (the universal standard reference), which covers this topic identically to Sembulingam. All major headings match Sembulingam's chapter structure.

Mechanism of Muscular (Skeletal Muscle) Contraction

1. Physiological Anatomy - Quick Review

2. Molecular Structure of Contractile Proteins

Myosin Filament

• Molecular weight ~480,000
• Consists of two intertwined heavy chains forming a tail and two globular heads
• The heads project outward as cross-bridges
• Each myosin head has:
  • An actin-binding site
  • An ATPase active site (splits ATP to provide energy)

Actin Filament

• Two strands of F-actin (fibrous actin) wound in a double helix
• Each F-actin strand is a polymer of G-actin (globular actin) monomers
• Each G-actin monomer has an active site that binds to myosin cross-bridge
• Two regulatory proteins sit in the grooves of the actin helix:
  • Tropomyosin - a long filamentous protein that physically blocks the actin active sites at rest
  • Troponin complex - attached to tropomyosin; has 3 subunits: TnI (inhibitory), TnT (tropomyosin-binding), TnC (Ca²⁺-binding)

3. Neuromuscular Transmission (Initiating the Contraction)

1. A nerve action potential reaches the motor nerve terminal
2. Acetylcholine (ACh) is released from synaptic vesicles into the neuromuscular junction
3. ACh binds to nicotinic receptors on the motor end plate
4. The end plate potential is generated → triggers a muscle action potential
5. The action potential spreads along the sarcolemma and down the T-tubules (transverse tubules)

4. Excitation-Contraction Coupling

1. The action potential travels along the T-tubule system deep into the muscle fibre
2. T-tubules are in close contact with the lateral sacs (terminal cisternae) of the sarcoplasmic reticulum (SR) at the triad
3. Depolarization activates dihydropyridine (DHP) receptors in the T-tubule wall, which are mechanically coupled to ryanodine receptors (RyR1) on the SR
4. RyR1 opens → massive release of Ca²⁺ from the SR into the sarcoplasm
5. Ca²⁺ concentration rises from ~0.1 µmol/L (resting) to >10 µmol/L

5. Sliding Filament Theory (Huxley, 1954)

• Actin filaments are pulled inward among the myosin filaments
• The Z discs are pulled toward each other
• The I band narrows, the H zone disappears, but the A band length stays constant
• The sarcomere shortens → the whole muscle shortens

6. Cross-Bridge Cycling Mechanism ("Walk-Along" Theory)

• Released Ca²⁺ binds to TnC of the troponin complex
• This causes a conformational change in tropomyosin, which shifts it away from the actin active sites
• The active sites on actin are now exposed

• The myosin head (already cocked, carrying ADP + Pi) binds to the exposed actin active site
• An actin-myosin cross-bridge is formed

• The myosin head tilts/pivots ~45°, pulling the actin filament toward the centre of the sarcomere
• This is the power stroke - ADP + Pi are released
• The myosin head is now in the "low-energy" position (pointing at ~45°)

• A new ATP molecule binds to the myosin head
• This causes the cross-bridge to detach from actin
• If no new ATP → permanent cross-bridge = rigor mortis

• ATP is hydrolyzed to ADP + Pi by the myosin ATPase
• The energy is stored, and the myosin head returns to the 90° (cocked) high-energy position
• The head is now ready to bind to a new actin site further along the filament

7. Relaxation

1. When nerve stimulation stops, Ca²⁺ is actively pumped back into the SR by the Ca²⁺-ATPase (SERCA) pump
2. Ca²⁺ concentration in sarcoplasm falls
3. Ca²⁺ dissociates from TnC
4. Tropomyosin shifts back to block actin active sites
5. Cross-bridge cycling stops → muscle relaxes

8. Role of ATP - Energy Sources

9. Summary Diagram (Sequence for 15-mark answer)

Nerve impulse
     ↓
ACh release → End plate potential
     ↓
Muscle action potential → T-tubule depolarization
     ↓
SR releases Ca²⁺
     ↓
Ca²⁺ binds TnC → Tropomyosin shifts → Actin sites exposed
     ↓
Myosin cross-bridge binds actin
     ↓
Power stroke (ADP+Pi released) → Actin slides inward
     ↓
ATP binds myosin → Cross-bridge detaches
     ↓
ATP hydrolysis → Myosin head cocks (re-energizes)
     ↓
Cycle repeats → Sarcomere shortens → Muscle contracts
     ↓
Ca²⁺ pumped back to SR → Tropomyosin re-blocks → Relaxation

Key Points to Mention for 15 Marks

1. Structural basis - sarcomere, A/I/H/Z bands, myosin & actin structure (2 marks)
2. Troponin-tropomyosin regulatory system (2 marks)
3. Neuromuscular junction + action potential (1 mark)
4. Excitation-contraction coupling / Ca²⁺ release from SR (2 marks)
5. Sliding filament theory - Huxley with what changes/what stays constant (2 marks)
6. Cross-bridge cycle - 5 steps in detail (4 marks)
7. Relaxation mechanism (1 mark)
8. Energy sources (1 mark)

• Guyton and Hall Textbook of Medical Physiology (relevant to Chapter 6 - Contraction of Skeletal Muscle)