Presynaptic calcium channels

At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca2+ entry through voltage-gated Ca2+ (Ca-V) 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 Ca(V)2 channel family (comprising Ca(V)2.1, Ca(V)2.2 and Ca(V)2.3 isoforms) encode the pore-forming alpha 1 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 Ca(V)2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed alpha 1 subunit of the Ca(V)2.1 as well as endogenous Ca(V)2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca2+-dependent modulation of Ca(V)2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy. (C) 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.