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Consequence of the presence of two different β subunit isoforms in a GABA A receptor
Author(s) -
Boulineau Nathalie,
Baur Roland,
Minier Frédéric,
Sigel Erwin
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03495.x
Subject(s) - receptor , cys loop receptors , gabaa receptor , etomidate , protein subunit , allosteric regulation , gabaa rho receptor , stimulation , chemistry , agonist , gene isoform , biochemistry , pentamer , g alpha subunit , xenopus , biology , endocrinology , pharmacology , acetylcholine receptor , gene , nicotinic acetylcholine receptor , propofol
The major isoforms of GABA A receptors are thought to be composed of two α, two β and one γ subunit(s). GABA A receptors containing two β 1 subunits respond differently to the anticonvulsive compound loreclezole and the general anaesthetic etomidate than receptors containing two β 2 subunits. Receptors containing β 2 subunits show a much larger allosteric stimulation by these agents than those containing β 1 subunits. We were interested to know how receptors containing both β 1 and β 2 subunits, in different positions respond to loreclezole and etomidate. To answer this question, subunits were fused at the DNA level to form dimeric and trimeric subunits. Concatenated receptors (α 1 ‐β 1 ‐α 1 /γ 2 ‐β 1 , α 1 ‐β 2 ‐α 1 /γ 2 ‐β 1 , α 1 ‐β 1 ‐α 1 /γ 2 ‐β 2 and α 1 ‐β 2 ‐α 1 /γ 2 ‐β 2 ) were expressed in Xenopus ooctyes and functionally compared in their response to the agonist GABA and to the positive allosteric modulators, loreclezole and etomidate. We have shown that (I) in the presence of both β 1 and β 2 subunits in the same pentamer (mixed receptors) direct gating by etomidate is similar to exclusively β 1 containing receptors; (II) In mixed receptors, stimulation by etomidate assumed characteristics intermediate to exclusively β 1 or β 2 containing receptors, but the values for the concentrations < 10 µ m were always much closer to those observed in α 1 ‐β 1 ‐α 1 /γ 2 ‐β 1 receptors; and (III) mixed receptors show no positional effects.