Recently, the structure of the alcohol pocket in a pentameric ion channel ortholog from the bacterium Gloeobacter violaceus (GLIC) (alcohol sensitized variant F14′A) revealed that GLIC shares many features with the alcohol pocket in GIRK channels (Sauguet et al., 2013). Specifically, the ethanol response of both GIRK and GLIC F14′A channels is altered when the volume of the alcohol pockets are altered with side chains of varying volume (Aryal et al., 2009; Sauguet et al., 2013). Another common feature of the pocket is the placement near a structural or gating transition point. In GIRK channels, the alcohol pocket is located at the interface of two adjacent subunits, whereby the βD-βE and βL-βM loops move apart from each other during Gβγ-dependent activation (Finley et al., 2004; Whorton and MacKinnon, 2011). Similarly, the alcohol pocket in GLIC F14′A is located in an intersubunit crevice close to the transmembrane domain (M2), which undergoes a conformational rotation during channel activation (Sauguet et al., 2013). Thus, in both channels, alcohol may serve as an allosteric modulator. Lastly, the chemical interactions of alcohol in the pocket
