title: Emerging evidence for specific neuronal functions of auxiliary calcium channel α₂δ subunits.
abstract: 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.
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Geisler
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Clemens L
authors.initials: CL
authors.lastname: Schöpf
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D019317:Evidence-Based Medicine; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D021122:Protein Subunits; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D021122:Protein Subunits