Chunk #19 — Acute effects of ethanol on GABAA receptors — Direct effects on GABAA receptor subtypes — High dose effects of ethanol (>30 mM) on tonic inhibition
The discrepancies in ethanol actions observed across various laboratories may indicate very specific requirements for low dose effects of ethanol on extrasynaptic GABAA receptors. It is also possible that presynaptic ethanol actions may play a role. Recent studies suggest that increased firing onto cerebellar granule cells increases extrasynaptically available GABA (Botta et al. 2007b; Carta et al. 2004; Valenzuela et al. 2005) that may contribute to changes in tonic inhibition. Other mechanisms may include increases in endogenous modulators that are particularly potent at extrasynaptic GABAA receptors. Ethanol increases GABAergic neuroactive steroids in slice preparations (see ‘Ethanol-induced elevation of neuroactive steroids’). Ethanol also increases taurine (De Witte et al. 1994), which has been shown to enhance tonic inhibition at low concentrations (Jia et al. 2008b). The possibility exists that other unknown chemicals are also released by ethanol. Alternatively, it is possible that the intracellular milieu of different preparations, including second messengers, kinases and phosphatases, may contribute to ethanol actions. Indeed, recent work by Choi et al. (2008) using knockout mice and stably transfected cells has shown that PKCδ activity may be
