Presynaptic calcium channels.

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