Alpha Subunit Position and GABA Receptor Function

doi:10.1126/stke.2702005pe5

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Sci. STKE, 8 February 2005
Vol. 2005, Issue 270, p. pe5
[DOI: 10.1126/stke.2702005pe5]

PERSPECTIVES

Alpha Subunit Position and GABA Receptor Function

David R. Burt^*

Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Summary: GABA_A ( ${gamma}$ -aminobutyric acid type A) receptors are ligand-gated ion channels composed of five subunits, generally two ${alpha}$ s, two ßs, and a ${gamma}$ 2. Recent research in which sets of subunits containing ${alpha}$ 1 or ${alpha}$ 6 subunits were artificially linked has revealed the importance of subunit position in determining GABA_A receptor function. Sensitivity to benzodiazepines depended on juxtaposition of an ${alpha}$ 1 subunit with the ${gamma}$ 2 subunit, whereas sensitivity to furosemide depended only on the presence of an ${alpha}$ 6 subunit and not on its specific location. The major utility of the linked subunit approach is to provide a mechanism for discovering the functional signatures of defined subunit arrangements, and thus a route to identifying such arrangements in vivo.