Presynaptic calcium channels

Abstract

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_V2 channel family (comprising Ca_V2.1, Ca_V2.2 and Ca_V2.3 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 Ca_V2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed α1 subunit of the Ca_V2.1 as well as endogenous Ca_V2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca²⁺-dependent modulation of Ca_V2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy.

Keywords: Ca(2+) binding proteins; Ca(2+) channels; G-proteins; Synaptic proteins; Synaptic transmission.