Functional biology of the α2δ subunits of voltage-gated calcium channels

In this review, we examine what is known about the mechanism of action of the auxiliary alpha(2)delta subunits of voltage-gated Ca(2+) (Ca(v)) channels. First, to provide some background on the alpha(2)delta proteins, we discuss the genes encoding these channels, in addition to the topology and predicted structure of the alpha(2)delta subunits. We then describe the effects of alpha(2)delta subunits on the biophysical properties of Cav channels and their physiological function. All alpha(2)delta) 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 alpha(2)delta 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 alpha(2)delta-1 and alpha(2)delta-2 subunits.