Mechanism of Skeletal Muscle Contraction

1. Events at the neuromuscular junction

1. An action potential reaches the terminal of an alpha motor neuron.
2. Voltage-gated Ca²⁺ channels open in the nerve terminal, causing Ca²⁺ entry.
3. Acetylcholine (ACh) is released into the synaptic cleft.
4. ACh binds to nicotinic receptors on the motor end plate and opens ligand-gated cation channels.
5. Predominant Na⁺ influx produces an end-plate potential. If threshold is reached, a muscle action potential is generated.
6. ACh is rapidly destroyed by acetylcholinesterase.

2. Excitation-contraction coupling

1. The muscle action potential spreads over the sarcolemma and travels deep into the muscle fibre through the transverse (T) tubules.
2. Depolarization of the T tubules activates dihydropyridine receptors, which in turn open ryanodine receptor Ca²⁺ release channels of the terminal cisternae of the sarcoplasmic reticulum.
3. Large amounts of Ca²⁺ are released from the sarcoplasmic reticulum into the sarcoplasm.

3. Role of calcium and regulatory proteins

1. Ca²⁺ binds to troponin C on the thin filament.
2. This produces a conformational change in the troponin-tropomyosin complex.
3. Tropomyosin moves away from the active sites on actin.
4. The myosin-binding sites on actin are exposed, allowing actin-myosin cross-bridge formation.

4. Cross-bridge cycle

1. Attachment: Energized myosin head, carrying ADP and phosphate (Pi), binds to an exposed active site on actin.
2. Power stroke: Release of Pi and then ADP causes the myosin head to tilt. It pulls the actin filament toward the centre of the sarcomere.
3. Detachment: A fresh ATP molecule binds to the myosin head, causing it to detach from actin.
4. Reactivation: ATP is hydrolysed into ADP and Pi. The energy released re-cocks or energizes the myosin head, preparing it for another cycle.

• Cytosolic Ca²⁺ remains elevated
• ATP is available
• Active sites on actin remain exposed

5. Changes in the sarcomere

• Z lines move closer together.
• I band becomes shorter.
• H zone becomes narrower or may disappear.
• A band remains unchanged because the length of thick myosin filament does not change.
• The sarcomere shortens, producing muscle contraction.

6. Relaxation

1. Ca²⁺ is actively pumped back into the sarcoplasmic reticulum by the Ca²⁺-ATPase pump.
2. Cytosolic Ca²⁺ concentration falls.
3. Ca²⁺ dissociates from troponin C.
4. Tropomyosin again covers the myosin-binding sites on actin.
5. Cross-bridge cycling ceases and the muscle relaxes.

Rigor Mortis

Mechanism

1. ATP production ceases because oxidative metabolism stops.
2. Ca²⁺ leaks from the sarcoplasmic reticulum into the sarcoplasm.
3. Ca²⁺ exposes actin-binding sites and actin-myosin cross-bridges form.
4. However, in the absence of ATP, myosin heads cannot detach from actin.
5. Therefore, muscles remain in a fixed contracted and rigid state.