Ethanol has rapid acute effects on the function of proteins involved in excitatory and inhibitory synaptic transmission (Figures 1 and 2). Ethanol generally potentiates cys-loop ligand-gated ion channels (LGICs) (e.g., GABAA and glycine receptors [GlyRs]) but inhibits ionotropic glutamate receptors (reviewed in Lovinger and Roberto, 2013; Söderpalm et al., 2017). The different ligand-binding and transmembrane domains of these proteins likely underlie this difference. The current thinking is that ethanol interacts with membrane-spanning domains within these proteins and the subsequent allosteric changes in conformation produced differ for the different LGIC subtypes (Möykkynen and Korpi, 2012; Olsen et al., 2014). However, more work is needed to understand the structural basis of these differences. Ethanol also modulates nicotinic acetylcholine receptor (nAChR) function in a subunit-specific manner (Davis and de Fiebre, 2006; Hendrickson et al., 2013; Rahman et al., 2016) and potentiates 5HT3Rs (McBride et al., 2004).
