Neurotransmitter Release

Synaptic vesicle exocytosis is rapid and highly localized, which are features that arise from the organization of the presynaptic active zone, where vesicle fusion occurs. Colocalization of calcium channels with the proteins making up the vesicle docking machinery at the active zone, combined with the low affinity and high cooperativity of the calcium sensor for vesicle fusion, allows vesicles to fuse with short delay after a presynaptic action potential. Evidence suggests that the calcium concentration driving synaptic vesicle fusion corresponds to the high level (50-100 muM) achieved only within the microdomain of elevated calcium near the inner mouth of open calcium channels. Retrieval of synaptic vesicle membrane by endocytosis is also regulated by internal calcium but at much lower concentrations. Endocytosis occurs rapidly after exocytosis if internal calcium is near the basal level but is inhibited by elevated internal calcium (0.5-1.0 muM).