Although these studies implicate the GIRK channel in alcohol binding, it remains unknown whether altering the GIRK channel composition or alcohol pocket chemistry will yield “alcohol-resistant” mutants. For example, future studies will need to identify mutations with the alcohol pocket of GIRK channels from human or closely related rat and mouse GIRK channels, which exhibit alcohol-deficient response but normal G protein gating. Such GIRK mutants can be used to create novel knock-in animals that do not develop alcohol-related behavioral changes or alcohol addiction. Furthermore, it is predicted that such knock-in animals will have fewer phenotypic side effects due to unaltered G protein response. On the other hand, altering the alcohol pocket chemistry in GIRK channels can enhance ethanol response, which would be an unwanted side-effect. This finding highlights the intricate chemical and physical nature of the alcohol pocket in GIRK channel.
