Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology.

Annette C Dolphin

doi:10.1113/jp272262

Abstract

Voltage‐gated calcium channels are essential players in many physiological processes in excitable cells. There are three main subdivisions of calcium channel, defined by the pore‐forming α1 subunit, the CaV1, CaV2 and CaV3 channels. For all the subtypes of voltage‐gated calcium channel, their gating properties are key for the precise control of neurotransmitter release, muscle contraction and cell excitability, among many other processes. For the CaV1 and CaV2 channels, their ability to reach their required destinations in the cell membrane, their activation and the fine tuning of their biophysical properties are all dramatically influenced by the auxiliary subunits that associate with them. Furthermore, there are many diseases, both genetic and acquired, involving voltage‐gated calcium channels. This review will provide a general introduction and then concentrate particularly on the role of auxiliary α2δ subunits in both physiological and pathological processes involving calcium channels, and as a therapeutic target.

Highlights

Excitable cells contain functional voltage-gated ion channels, including calcium channels
We identified that in the absence of a CaVβ subunit, Gβγ-mediated inhibition is still present, but it is not voltage dependent, meaning that it cannot be removed by preceding depolarization
We have found that the adaptor protein complex-1 (AP-1) is important for trafficking of CaV2.2 from the trans-Golgi network to the plasma membrane, via an alternatively spliced exon 37 in the proximal C-terminus

Summary

Introduction

Excitable cells contain functional voltage-gated ion channels, including calcium channels. Functional voltage-gated calcium channels are composed of pore-forming α1 subunit proteins, encoded by the CACNA1x genes (for review see Catterall et al 2003), of which there are 10 isoforms in the mammalian genome.

Results

Conclusion