Alpha subunit position and GABA receptor function.
GABA(A) (gamma-aminobutyric acid type A) receptors are ligand-gated ion channels composed of five subunits, generally two alphas, two betas, and a gamma2. Recent research in which sets of subunits containing alpha1 or alpha6 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 alpha1 subunit with the gamma2 subunit, whereas sensitivity to furosemide depended only on the presence of an alpha6 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.
Burt
David R
DR
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dburt@umaryland.edu
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D005665:Furosemide / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009865:Oocytes; D011485:Protein Binding; D055503:Protein Multimerization; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
C546240:GABRA1 protein, human; C546171:GABRA6 protein, human; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D001569:Benzodiazepines; D005665:Furosemide