Multiple Roles of Calcium Ions in the Regulation of Neurotransmitter Release

The intracellular calcium concentration ([Ca2+]) has important roles in the triggering of neurotransmitter release and the regulation of short-term plasticity (STP). Transmitter release is initiated by quite high concentrations within microdomains, while short-term facilitation is strongly influenced by the global buildup of “residual calcium.” A global rise in [Ca2+] also accelerates the recruitment of release-ready vesicles, thereby controlling the degree of short-term depression (STD) during sustained activity, as well as the recovery of the vesicle pool in periods of rest. We survey data that lead us to propose two distinct roles of [Ca2+] in vesicle recruitment: one accelerating “molecular priming” (vesicle docking and the buildup of a release machinery), the other promoting the tight coupling between releasable vesicles and Ca2+ channels. Such coupling is essential for rendering vesicles sensitive to short [Ca2+] transients, generated during action potentials.