Figure 29-1 The key ion channels involved in neuromuscular transmission and excitation contraction coupling. Nerve impulses arriving at the nerve terminal activate voltage-gated Ca²⁺ channels (1). The resulting increase in cytoplasmic Ca²⁺ concentration is essential in exocytosis of acetylcholine. Binding of acetylcholine to postsynaptic nicotinic cholinergic receptors activates an integral nonselective cation channel, which depolarizes the sarcolemmal membrane (2). Depolarizing the sarcolemma to threshold activates voltage-gated Na⁺ channels (3), which propagate action potential impulses deep into the muscle through the transverse tubule system. Within the transverse tubule system, L-type voltage-gated Ca²⁺ channels sense membrane depolarization and undergo a conformational change (4). A physical link between the α₁ -subunit and the ryanodine receptor is thought to transfer the signal to sarcoplasmic reticulum to induce the release of stored Ca²⁺ (5). (Adapted from Alberts B, Bray D, Lewis J, et al: Molecular Biology of the Cell, 3rd ed. New York, Garland Press, 1994.)