Chunk #23 — Acute effects of ethanol on GABAA receptors — Direct effects on GABAA receptor subtypes — High dose effects of ethanol (>30 mM) on phasic inhibition
A membrane-spanning region of the β3-GABAA receptor subunit is also implicated in GABAA receptor responses to higher amounts of ethanol. Work by Wallner et al. (2006) has indicated that while Ro15-4513 blocked ethanol-induced potentiation at low doses, higher concentrations of ethanol still enhanced GABAA receptor function in the presence of Ro15-4513. Mutations in equivalent positions in β1-GABAA receptors also modulate ethanol responses like intravenous anesthetic GABAA receptor modulators etomidate and propofol in β3-GABAA receptors (Jurd et al. 2003; Mihic et al. 1997). This evidence supports the notion that ethanol and Ro15-4513 may bind to the same site on GABAA receptors at low ethanol concentrations whereas a second ethanol-binding site involving α and β subunits may be responsible for ethanol responses at higher concentrations.
