Voltage-gated calcium channel α 2δ subunits: an assessment of proposed novel roles.

Voltage-gated calcium (CaV) channels are associated with β and α2δ auxiliary subunits. This review will concentrate on the function of the α2δ protein family, which has four members. The canonical role for α2δ subunits is to convey a variety of properties on the CaV1 and CaV2 channels, increasing the density of these channels in the plasma membrane and also enhancing their function. More recently, a diverse spectrum of non-canonical interactions for α2δ proteins has been proposed, some of which involve competition with calcium channels for α2δ or increase α2δ trafficking and others which mediate roles completely unrelated to their calcium channel function. The novel roles for α2δ proteins which will be discussed here include association with low-density lipoprotein receptor-related protein 1 (LRP1), thrombospondins, α-neurexins, prion proteins, large conductance (big) potassium (BK) channels, and N-methyl-d-aspartate (NMDA) receptors.