Control of neurotransmitter release: From Ca²⁺ to voltage dependent G-protein coupled receptors

This review discusses two theories that try to explain mechanisms of control of neurotransmitter release in fast synapses: the Ca²⁺ hypothesis and the Ca²⁺ voltage hypothesis. The review summarizes experimental results that are incompatible with predictions from the Ca ²⁺ hypothesis and concludes that Ca²⁺ is involved in the control of the amount of release but not in the control of the time course of evoked release, i.e., initiation and termination of evoked release. Results summarizing direct effects of changes in membrane potential on the release machinery are then presented. These changes in membrane potential affect the affinity (for the transmitter) of presynaptic autoinhibitory G-protein coupled receptors (GPCRs). The voltage dependence of these GPCRs and their pivotal role in determining the time course of evoked release is discussed.