title: Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels.
abstract: In this review, we examine what is known about the mechanism of action of the auxiliary alpha2delta subunits of voltage-gated Ca(2+) (Ca(v)) channels. First, to provide some background on the alpha2delta proteins, we discuss the genes encoding these channels, in addition to the topology and predicted structure of the alpha2delta subunits. We then describe the effects of alpha2delta subunits on the biophysical properties of Ca(v) channels and their physiological function. All alpha2delta 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 alpha2delta 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 alpha2delta-1 and alpha2delta-2 subunits.
authors.affiliation: Laboratory of Cellular and Molecular Neuroscience, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Davies
authors.forename: Jan
authors.initials: J
authors.lastname: Hendrich
authors.forename: Alexandra Tran
authors.initials: AT
authors.lastname: Van Minh
authors.forename: Jack
authors.initials: J
authors.lastname: Wratten
authors.forename: Leon
authors.initials: L
authors.lastname: Douglas
authors.forename: Annette C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D002524:Cerebellar Ataxia / Q000503:physiopathology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology; D000077206:Gabapentin; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D009437:Neuralgia / Q000503:physiopathology; D021122:Protein Subunits / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; C425903:CACNA2D1 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D021122:Protein Subunits; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin