Regulation of active zone ca2+ channel

Abstract

At the presynaptic active zone, Ca2+ influx through voltage-gated CaV2 channels triggers fast, synchronous neurotransmitter release from synaptic vesicles. Synaptic vesicles localized to release sites are tightly coupled with presynaptic CaV2 channels whereby neurotransmitter release is proportional to the Ca2+ current, or the Ca2+ concentration, with the third or fourth power. CaV2 channel activity is regulated directly or indirectly by multiple mechanisms through protein-protein interactions, before and after synaptic vesicle exocytosis, resulting in fine-tuning of Ca2+ entry that effectively modulates basal neurotransmitter release and underlies presynaptic shortterm plasticity. Presynaptic active zone proteins form a large complex, which tether CaV2 channels, dock and prime synaptic vesicles at release sites, and possess regulatory function. CaV2 channel modulation, which is upstream of synaptic vesicle exocytosis, that leads to changes in Ca2+ influx provides a powerful and efficient way to regulate synaptic transmission. In this chapter, we review progress toward understanding the cellular and molecular mechanisms that modulate the activity of Ca2+ channels at the presynaptic active zone. A remaining challenge is to understand how these processes work together to shape synaptic transmission and synaptic plasticity.