During muscle contraction, which event triggers the release of calcium from the sarcoplasmic reticulum?

• A. Voltage‑sensitive proteins in the T‑tubules change shape in response to an action potential
• B. Acetylcholine binds to receptors on the sarcolemma
• C. ATP hydrolysis by myosin
• D. Sodium influx into the muscle cell

Answer: (A)

Calcium release from the sarcoplasmic reticulum is triggered by depolarization detected by voltage-sensitive proteins in the T-tubules. When an action potential travels along the membrane, the voltage-sensitive channels in the T-tubule membrane (DHPR) change shape and mechanically couple to the ryanodine receptors on the SR, opening them and releasing Ca2+ into the cytosol. The sudden rise in intracellular Ca2+ allows troponin C to bind calcium, causing tropomyosin to move away from actin's myosin-binding sites and enabling cross-bridge cycling with ATP hydrolysis. The initial trigger for this calcium release is the membrane depolarization sensed by the T-tubule voltage sensors, not the acetylcholine binding itself, the ATPase activity of myosin, or sodium influx.