Presynaptic calcium channels

At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca2+ entry through voltage-gated Ca2+ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca2+ channels form a large signaling complex, which targets synaptic vesicles to Ca2+ channels for efficient release and mediates Ca2+ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation. Modulation of presynaptic Ca2+ channels has a powerful influence on synaptic transmission. This article overviews spatial and temporal regulation of Ca2+ channels by effectors and sensors of Ca2+ signaling, and describes the emerging evidence for a critical role of Ca2+ channel regulation in control of synaptic transmission and presynaptic plasticity. Sympathetic superior cervical ganglion neurons in culture expressing CaV2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed α1 subunit of the CaV2.1 as well as endogenous CaV2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca2+-dependent modulation of CaV2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy.