Muscle Contraction Mechanism: Step-by-Step from Action Potential to Relaxation

Skeletal muscle contraction follows a precise sequence of electrophysiologic and molecular events—the excitation-contraction coupling cycle.

Nine-Step Contraction Cycle

1. Motor neuron action potential arrives at neuromuscular junction (NMJ).
2. ACh release: Voltage-gated Ca²⁺ channels open → vesicle fusion → acetylcholine into synaptic cleft.
3. ACh binding: Nicotinic receptors on motor endplate → Na⁺ influx → endplate potential (depolarization).
4. Muscle fiber action potential: Endplate potential spreads via T-tubules (invaginations of sarcolemma).
5. Ca²⁺ release: T-tubule depolarization → DHPR conformational change → RyR1 opening on SR → Ca²⁺ flood.
6. Troponin binding: Ca²⁺ binds troponin-C → tropomyosin shift → exposes myosin-binding sites on actin.
7. Cross-bridge cycling: Myosin heads bind actin → power stroke (ADP/Pi release) → ATP binds → detachment → reset.
8. Sarcomere shortening: Thin filaments slide past thick filaments → Z-discs approach → force generation.
9. Relaxation: SR Ca²⁺-ATPase (SERCA) pumps Ca²⁺ back → troponin-tropomyosin blocks sites → cross-bridges detach → passive/active lengthening.

Energy & Regulation

• ATP roles: Myosin ATPase (cycling), SERCA (reuptake), Na⁺/K⁺-ATPase (membrane potential).
• Fatigue factors: Pi accumulation, H⁺, ROS, glycogen depletion, SR Ca²⁺ leak.
• Motor unit recruitment: Size principle (small → large) grades force.

Clinical Correlates

• Myasthenia gravis: AChR antibodies → NMJ failure.
• Malignant hyperthermia: RyR1 mutation → uncontrolled Ca²⁺ release.
• Periodic paralyses: Na⁺/K⁺ channel mutations → excitability defects.