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© Research
Publication : Trends in Pharmacological Sciences

Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Trends in Pharmacological Sciences - 01 May 2007

Anthony Davies; Jan Hendrich; Alexandra Tran Van Minh; Jack Wratten; Leon Douglas; Annette C. Dolphin

Link to Pubmed [PMID] – 17403543

Trends Pharmacol Sci. 2007 May;28(5):220-8

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.