G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action

C-protein-coupled inwardly rectifying potassium channels (GIRKs) are import ant for regulation of synaptic transmission and neuronal firing rates. Beca use of their key role in brain function, we asked if these potassium channe ls are targets of alcohol action. Ethanol enhanced function of cerebellar g ranule cell GIRKs coupled to GABA(B) receptors. Enhancement of GIRK functio n by ethanol was studied in detail using Xenopus oocytes expressing homomer ic or heteromeric channels. Function of all GIRK channels was enhanced by i ntoxicating concentrations of ethanol, but other, related inwardly rectifyi ng potassium channels were not affected. GIRK2/IRK1 chimeras and GIRK2 trun cation mutants were used to identify a region of 43 amino acids in the carb oxyl (C) terminus that is critical for the action of ethanol on these chann els.