A threonine residue in the M2 region of the β1 subunit is needed for expression of functional α1β1 GABAA receptors

被引：7

作者：

Dalziel, JE ^{[1
]}

Birnir, B ^{[1
]}

Everitt, AB ^{[1
]}

Tierney, ML ^{[1
]}

Cox, GB ^{[1
]}

Gage, PW ^{[1
]}

机构：

[1] Australian Natl Univ, John Curtin Sch Med Res, Membrane Biol Program, Canberra, ACT 2601, Australia

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 370卷 / 03期

关键词：

M2 transmembrane segment; ligand-gated; GABA(A); receptor; human; Sf9; cell; desensitization; receptor assembly;

D O I：

10.1016/S0014-2999(99)00138-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Although then is a high degree of homology in the M2 transmembrane segments of alpha(1) and beta(1) subunits, subunit-specific effects were observed in alpha(1)beta(1) GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta(1) subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha(1) subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：345 / 348

页数：4

共 23 条

[1] GABA(A) RECEPTOR NEEDS 2 HOMOLOGOUS DOMAINS OF THE BETA-SUBUNIT FOR ACTIVATION BY GABA BUT NOT BY PENTOBARBITAL [J].