Many ligand-gated ion channels, such as those gated by gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), glycine, acetylcholine and serotonin, are responsive to ethanol (EtOH) and other alcohols1-4. Initially, alcohol was hypothesized to indirectly alter the function of channels by changing the fluidity of the lipid bilayer5. More recent studies, however, suggest alcohol acts directly through a physical-binding pocket located in the channel protein3,6. In addition to ligand-gated channels, alcohols also modulate potassium channels7-9. For example, EtOH activates G protein-gated inwardly rectifying potassium (GIRK or Kir3) channels7,8. Behavioral studies have shown that mice lacking GIRK2 channels exhibit diminished EtOH-dependent analgesia10 and consume more EtOH than wild-type mice11, suggesting a functional role for GIRK channels in response to alcohols in vivo.
