The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion (exocytosis). Within the presynaptic nerve terminal, vesicles containing neurotransmitter are localized near the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels at the down stroke of the action potential (tail current). Calcium ions then bind to synaptotagmin proteins found within the membranes of the synaptic vesicles, allowing the vesicles to fuse with the presynaptic membrane. The fusion of a vesicle is a stochastic process, leading to frequent failure of synaptic transmission at the very small synapses that are typical for the central nervous system. Large chemical synapses (e.g. the neuromuscular junction), on the other hand, have a synaptic release probability, in effect, of 1. Vesicle fusion is driven by the action of a set of proteins in the presynaptic terminal known as SNAREs. As a whole, the protein complex or structure that mediates the docking and fusion of presynaptic vesicles is called the active zone. The membrane added by the fusion process is later retrieved by endocytosis and recycled for the formation of fresh neurotransmitter-filled vesicles.
An exception to the general trend of neurotransmitter release by vesicular fusion is found in the type II receptor cells of  mammalian taste buds. Here the neurotransmitter ATP is released directly from the cytoplasm into the synaptic cleft via voltage gated channels.