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

doi:10.1038/nn1813

A new naturally occurring GABA_A 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 journal › Article › peer-review

209 Scopus citations

Abstract

According to the rules of GABA_A receptor (GABA_AR) subunit assembly, α4 and α6 subunits are considered to be the natural partners of δ subunits. These GABA_ARs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABA_AR 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 GABA_ARs 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 GABA_AR subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.

Original language	English (US)
Pages (from-to)	40-48
Number of pages	9
Journal	Nature Neuroscience
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/nn1813
State	Published - Jan 2007
Externally published	Yes

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Neuroscience(all)

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title = "A new naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol",

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.",

author = "Joseph Glykys and Zechun Peng and Dev Chandra and Homanics, {Gregg E.} and Houser, {Carolyn R.} and Istvan Mody",

note = "Funding Information: We thank W. Sieghart (Medical Univ. of Vienna, Austria) and J.-M. Fritschy (Univ. Z{\"u}rich, Switzerland) for the gifts of the GABAAR antibodies, and R.W. Olsen (UCLA) for helpful discussions. This project was supported by the Gonda",

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AU - Houser, Carolyn R.

AU - Mody, Istvan

N1 - Funding Information: We thank W. Sieghart (Medical Univ. of Vienna, Austria) and J.-M. Fritschy (Univ. Zürich, Switzerland) for the gifts of the GABAAR antibodies, and R.W. Olsen (UCLA) for helpful discussions. This project was supported by the Gonda

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N2 - 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.

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

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