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Skeletal muscle contraction follows the sliding filament model: thin actin filaments slide over thick myosin filaments, shortening each sarcomere without changing the filament lengths. Excitation-contraction coupling begins when muscle action potentials propagate along T-tubules, triggering Ca²⁺ release from the sarcoplasmic reticulum via ryanodine receptors. Ca²⁺ binds troponin C on the thin filament, causing tropomyosin to shift and expose myosin-binding sites on actin. Myosin heads undergo the cross-bridge cycle: bind actin → power stroke (ADP + Pi released) → rigor state → ATP binds → myosin detaches and re-cocks. Relaxation requires SERCA pumps (ATP-driven) to remove Ca²⁺ back into the sarcoplasmic reticulum, allowing tropomyosin to re-cover actin sites.
Memorize the four-step cross-bridge cycle with ion and nucleotide states at each step: cocked myosin (ATP hydrolyzed, ADP+Pi bound) → binds actin → power stroke (Pi released) → rigor state → ATP binds → detachment. Explain rigor mortis mechanically: ATP is depleted after death, so myosin cannot detach from actin — muscles lock rigid. Then draw a sarcomere at rest and at maximum contraction, labeling A, I, H, and M bands.
Skeletal muscle contraction is a beautiful example of molecular machinery scaled from individual protein interactions to whole-body movement. To understand it, start with the architecture: each muscle fiber is packed with myofibrils, and each myofibril is a repeating chain of sarcomeres. A sarcomere is bounded by Z-discs, from which thin (actin) filaments project inward. Thick (myosin) filaments occupy the center. Contraction happens when actin slides over myosin — the filaments themselves stay the same length, but the sarcomere shortens as overlap increases.
The trigger for contraction comes from your nervous system. An action potential travels down the motor neuron, crosses the neuromuscular junction (which you studied as a prerequisite), and generates an end-plate potential in the muscle membrane. This propagates as a muscle action potential along the fiber surface and then dips deep into the fiber via T-tubules. At junctions between T-tubules and the sarcoplasmic reticulum (SR), voltage-sensing proteins (dihydropyridine receptors) detect the action potential and physically gate ryanodine receptors in the SR membrane, releasing a flood of Ca²⁺ into the cytoplasm. This is excitation-contraction coupling — converting the electrical signal into a chemical trigger for the contractile machinery.
Ca²⁺ is the master switch for the thin filament. At rest, tropomyosin physically blocks the myosin-binding sites on actin. When Ca²⁺ binds to troponin C (part of the troponin complex), a conformational change shifts tropomyosin out of the way, exposing the binding sites. Myosin heads — already cocked and loaded with ADP + Pi from the previous hydrolysis — can now bind actin. Binding triggers release of Pi, followed by the power stroke: the myosin head pivots, pulling the actin filament toward the sarcomere center. ADP is released, leaving myosin in the rigor state. When a new ATP binds, myosin detaches; ATP hydrolysis re-cocks the head; and the cycle repeats as long as Ca²⁺ keeps troponin permissive.
Relaxation requires active work: SERCA pumps (Ca²⁺-ATPases in the SR membrane) use ATP to pump Ca²⁺ back into the SR against its concentration gradient. As cytoplasmic Ca²⁺ falls, troponin releases Ca²⁺, tropomyosin re-covers the actin sites, and myosin heads can no longer bind. This is why ATP is needed not just for the power stroke but for relaxation too — a point rigor mortis makes starkly: when ATP is exhausted after death, SERCA stops pumping, Ca²⁺ remains elevated, and myosin remains locked onto actin, stiffening the muscle.