pocket appears to be conserved within the family of inwardly rectifying potassium channels and across different species (Supplemental Figure S1). The effect of alcohol in the pocket may not produce the same effect on all Kir channels. For example, Kir2 and Kir1 channels are inhibited or unaffected by alcohols, while GIRK channels are activated (Kobayashi et al., 1999; Lewohl et al., 1999). In addition, a L257W mutation in the GIRK alcohol pocket alters alcohol activation but the analogous mutation in Kir2 channels (L245W) produces little effect on alcohol modulation of Kir2 channels. Furthermore, several other mutations to the Kir2 alcohol pocket (specifically F47W, L232W, and L330W) do not alter modulation by alcohols (Aryal et al., 2009). Many of these analogous mutations in GIRK channels render the channel non-functional, however, precluding determination of alcohol sensitivity.
