Functional biology of the α 2 δ subunits of voltage-gated calcium channels

In this review, we examine what is known about the mechanism of action of the auxiliary α 2 δ subunits of voltage-gated Ca 2+ (Ca v ) channels. First, to provide some background on the α 2 δ proteins, we discuss the genes encoding these channels, in addition to the topology and predicted structure of the α 2 δ subunits. We then describe the effects of α 2 δ subunits on the biophysical properties of Ca v channels and their physiological function. All α 2 δ subunits increase the density at the plasma membrane of Ca 2+ channels activated by high voltage, and we discuss what is known about the mechanism underlying this trafficking. Finally, we consider the link between α 2 δ subunits and disease, both in terms of spontaneous and engineered mouse mutants that show cerebellar ataxia and spike-wave epilepsy, and in terms of neuropathic pain and the mechanism of action of the gabapentinoid drugs - small-molecule ligands of the α 2 δ-1 and α 2 δ-2 subunits. © 2007 Elsevier Ltd. All rights reserved.

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