Calcium Channel α2δ Subunits: Structure, Functions and Target Site for Drugs

In this review we describe the genes encoding α2δ subunits, their topology and predicted structure. We then review the electrophysiological effects of α2δ subunits. It is clear from most studies that α2δ subunits increase channel density at the plasma membrane, but there is less agreement between studies and between channel subtypes concerning the effects of α2δ subunits on voltage-dependence of activation and inactivation. Most studies agree that α2δ subunits increase the kinetics of inactivation, for a number of different calcium channel subtypes. We also discuss the link between α2δ subunits and disease, particularly in terms of Ducky, the spontaneously occurring mutant mouse strain that has mutations in α2δ-2, and exhibits cerebellar ataxia and absence epilepsy. Finally, we will examine the evidence that α2δ subunits are the site of action of the anti-epileptic, anti-nociceptive drug gabapentin.