Emerging evidence for specific neuronal functions of auxiliary calcium channel α2δ subunits

Year, pages: 2015, 105 - 118

In nerve cells the ubiquitous second messenger calcium regulates a variety of vitally important functions including neurotransmitter release, gene regulation, and neuronal plasticity. The entry of calcium into cells is tightly regulated by voltage-gated calcium channels, which consist of a heteromultimeric complex of a pore forming α1, and the auxiliary β and α2δ subunits. Four genes (Cacna2d1-4) encode for the extracellular membrane-attached α2δ subunits (α2δ-1 to α2δ-4), out of which three isoforms (α2δ-1 to -3) are strongly expressed in the central nervous system. Over the years a wealth of studies has demonstrated the classical role of α2δ subunits in channel trafficking and calcium current modulation. Recent studies in specialized neuronal cell systems propose roles of α2δ subunits beyond the classical view and implicate α2δ subunits as important regulators of synapse formation. These findings are supported by the identification of novel human disease mutations associated with α2δ subunits and by the fact that α2δ subunits are the target of the anti-epileptic and anti-allodynic drugs gabapentin and pregabalin. Here we review the recently emerging evidence for specific as well as redundant neuronal roles of α2δ subunits and discuss the mechanisms for establishing and maintaining specificity.

Geisler, S., Schöpf, C., Obermair, G. 2015. Emerging evidence for specific neuronal functions of auxiliary calcium channel α2δ subunits. In General Physiology and Biophysics, vol. 34, no.2, pp. 105-118. 0231-5882.

Geisler, S., Schöpf, C., Obermair, G. (2015). Emerging evidence for specific neuronal functions of auxiliary calcium channel α2δ subunits. General Physiology and Biophysics, 34(2), 105-118. 0231-5882.