@article {Borghese1360, author = {Cecilia M. Borghese and Signe {\'\i} St{\'o}rustovu and Bjarke Ebert and Murray B. Herd and Delia Belelli and Jeremy J. Lambert and George Marshall and Keith A. Wafford and R. Adron Harris}, title = {The δ Subunit of γ-Aminobutyric Acid Type A Receptors Does Not Confer Sensitivity to Low Concentrations of Ethanol}, volume = {316}, number = {3}, pages = {1360--1368}, year = {2006}, doi = {10.1124/jpet.105.092452}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {GABAA receptors (GABAARs) are usually formed by α, β, and γ or δ subunits. Recently, δ-containing GABAARs expressed in Xenopus oocytes were found to be sensitive to low concentrations of ethanol (1{\textendash}3 mM). Our objective was to replicate and extend the study of the effect of ethanol on the function of α4β3δ GABAARs. We independently conducted three studies in two systems: rat and human GABAARs expressed in Xenopus oocytes, studied through two-electrode voltage clamp; and human GABAARs stably expressed in the fibroblast L(tk{\textendash}) cell line, studied through patch-clamp electrophysiology. In all cases, α4β3δ GABAARs were only sensitive to high concentrations of ethanol (100 mM in oocytes, 300 mM in the cell line). Expression of the δ subunit in oocytes was assessed through the magnitude of the maximal GABA currents and sensitivity to zinc. Of the three rat combinations studied, α4β3 was the most sensitive to ethanol, isoflurane, and 5α-pregnan-3α,21-diol-20-one (THDOC); α4β3δ and α4β3γ2S were very similar in most aspects, but α4β3δ was more sensitive to GABA, THDOC, and lanthanum than α4β3γ2S GABAARs. Ethanol at 30 mM did not affect tonic GABA-mediated currents in dentate gyrus reported to be mediated by GABAARs incorporating α4 and δ subunits. We have not been able to replicate the sensitivity of α4β3δ GABAARs to low concentrations of ethanol in four different laboratories in independent studies. This suggests that as yet unidentified factors may play a critical role in the ethanol effects on δ-containing GABAARs.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/316/3/1360}, eprint = {https://jpet.aspetjournals.org/content/316/3/1360.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }