Muscle Contraction: The Sliding Filament Mechanism of Actin and Myosin

Skeletal muscle contraction is driven by the cyclic interaction of two contractile proteins: actin (thin filament) and myosin (thick filament). This sliding filament mechanism is the fundamental basis of all voluntary movement.

Structural Organization

• Muscle Fiber: Multinucleated cell containing myofibrils.
• Sarcomere: Functional unit (Z-disc to Z-disc). Contains overlapping actin and myosin filaments.
• Thin Filament: Actin (globular G-actin polymerized to F-actin), tropomyosin, troponin complex (TnC, TnI, TnT).
• Thick Filament: Myosin II (two heavy chains, four light chains). Myosin heads (cross-bridges) project outward.

Contraction Cycle (Cross-Bridge Cycling)

1. Resting State: Tropomyosin blocks myosin-binding sites on actin. Troponin complex holds tropomyosin in place.
2. Excitation-Contraction Coupling: Action potential → T-tubules → sarcoplasmic reticulum (SR) releases Ca²⁺.
3. Ca²⁺ Binding: Ca²⁺ binds troponin C (TnC) → conformational change → tropomyosin shifts → exposes myosin-binding sites on actin.
4. Cross-Bridge Formation: Myosin head (with ADP·Pi bound) binds actin → strong binding.
5. Power Stroke: Release of Pi triggers myosin head rotation → pulls actin toward M-line (center of sarcomere). ADP released.
6. ATP Binding: New ATP binds myosin head → dissociation from actin.
7. ATP Hydrolysis: Myosin ATPase hydrolyzes ATP → ADP·Pi → "cocks" myosin head back to high-energy state.
8. Cycle Repeats: As long as Ca²⁺ and ATP are present, cycles continue → sarcomere shortens.

Relaxation

Ca²⁺ actively pumped back into SR by SERCA pumps → Ca²⁺ dissociates from troponin → tropomyosin re-covers binding sites → cross-bridges cannot form → elastic titin filaments and antagonistic muscles restore length.

Energy & Regulation

• ATP: Required for both power stroke (indirectly via hydrolysis) and cross-bridge detachment.
• Creatine Phosphate: Rapid ATP regeneration.
• Glycolysis/Oxidative Phosphorylation: Sustained ATP supply.
• Motor Unit Recruitment & Firing Rate: Nervous system controls force gradation.