suggesting that alcohol also stabilizes an open state (Sauguet et al., 2013). An attractive feature of an allosteric model for gating is that it is compatible with (1). low affinity of GIRK channels for alcohol, (2). low binding energy associated with alcohol-dependent activation of GIRK, and (3). apparent lack of chemical specificity for alcohols that can be accommodated within the GIRK alcohol pocket (Harris et al., 2008). How it is that alcohol- and Gβγ-dependent activation mechanisms are independent yet have partially overlapping binding sites remains an important question for future studies.
