FIGURE 22-29 Sequential activation of gated ion channels at a neuromuscular junction. Arrival of an action potential at the terminus of a presynaptic motor neuron induces opening of voltage-gated Ca²⁺ channels in the neuron (step 1) and subsequent release of acetylcholine, which triggers opening of the ligand-gated acetylcholine receptors in the muscle plasma membrane (step 2). The open receptor channel allows an influx of Na⁺ and an efflux of K⁺ from the muscle cell. The Na⁺ influx produces a localized depolarization of the membrane, leading to opening of voltage-gated Na⁺ channels and generation of an action potential (step 3). When the spreading depolarization reaches transverse tubules, it is sensed by voltage-gated Ca²⁺ channels in the plasma membrane. Through an unknown mechanism (indicated as ?) these channels remain closed but influence Ca²⁺ channels in the sarcoplasmic reticulum membrane (a network of membrane-bound compartments in muscle), which release stored Ca²⁺ into the cytosol (step 4). The resulting rise in cytosolic Ca²⁺ causes muscle contraction by mechanisms discussed in Chapter 17.