Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels.
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.
Davies
Anthony
A
Laboratory of Cellular and Molecular Neuroscience, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Hendrich
Jan
J
Van Minh
Alexandra Tran
AT
Wratten
Jack
J
Douglas
Leon
L
Dolphin
Annette C
AC
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
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