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

Joseph Glykys, Zechun Peng, Dev Chandra, Gregg E. Homanics, Carolyn R. Houser, Istvan Mody

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

According to the rules of GABAA receptor (GABAAR) subunit assembly, α4 and α6 subunits are considered to be the natural partners of δ subunits. These GABAARs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: δ subunits of hippocampal interneurons are coexpressed and colocalized with α1 subunits, but not with α4, α6 or any other α subunits. Ethanol potentiates the tonic inhibition mediated by such native α1/δ GABAARs in wild-type and in α4 subunit-deficient (Gabra4-/-) mice, but not in δ subunit-deficient (Gabrd-/-) mice. We also ruled out any compensatory upregulation of α6 subunits that might have accounted for the ethanol effect in Gabra4-/- mice. Thus, α1/δ subunit assemblies represent a new neuronal GABAAR subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalNature Neuroscience
Volume10
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience

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