Chunk #17 — Acute effects of ethanol on GABAA receptors — Direct effects on GABAA receptor subtypes — High dose effects of ethanol (>30 mM) on tonic inhibition
While the previously described studies have indicated a major role of ethanol potentiation of GABA inhibition at α4/6βδ extrasynaptic receptors, these observations are controversial. In a recent study by Borghese et al. (2006a), rat and human α4β3δ-GABAA subunits expressed in oocytes, α4β3δ subunits stably transfected in fibroblasts, and slice recordings conducted in dentate granule cells all failed to exhibit enhanced GABAA receptor potentiation by low doses of ethanol. Further, effects of lower doses of ethanol (30 mM or less) are not observed in cerebellar granule cells (Casagrande et al. 2007; Yamashita et al. 2006) or ventrobasal thalamic neurons (Jia et al. 2008a) and dentate gyrus granule cells that express α4β2δ receptors (Liang et al. 2008). However, the latter study did observe some detectable effects at 10 mM ethanol. One possibility may be the orientation of receptor subunits within the GABAA receptor pentamer. However, Kaur et al. (2009) have shown that 30 mM ethanol did not display potentiation in concatenated α1β3δ receptors. In agreement with the lack of a low dose effect, autoradiographic experiments also suggest that Ro15-4513 binding is not
