A new naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol

被引：201

作者：

Glykys, Joseph

Peng, Zechun

Chandra, Dev

Homanics, Gregg E.

Houser, Carolyn R.

Mody, Istvan ^{[1
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA

[4] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA

[5] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA

[6] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA

来源：

NATURE NEUROSCIENCE | 2007年 / 10卷 / 01期

关键词：

D O I：

10.1038/nn1813

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

According to the rules of GABA(A) receptor (GABA(A)R) subunit assembly, alpha 4 and alpha 6 subunits are considered to be the natural partners of delta subunits. These GABA(A)Rs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: d subunits of hippocampal interneurons are coexpressed and colocalized with alpha 1 subunits, but not with alpha 4, alpha 6 or any other alpha subunits. Ethanol potentiates the tonic inhibition mediated by such native alpha 1/delta GABA(A)Rs in wild-type and in alpha 4 subunit-deficient (Gabra4(-/-)) mice, but not in delta subunit - deficient (Gabrd(-/-)) mice. We also ruled out any compensatory upregulation of alpha 6 subunits that might have accounted for the ethanol effect in Gabra4(-/-) mice. Thus, alpha 1/delta subunit assemblies represent a new neuronal GABA(A)R subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.

引用

页码：40 / 48

页数：9

共 52 条

[41] Hormonally regulated α4β2δ GABAA receptors are a target for alcohol [J].