GIRK channels are emerging as a potential drug target for treating alcoholism and other neurological disorders3. Interestingly, chronic alcohol exposure leads to increased cholesterol levels and more widespread distribution of cholesterol in the membrane leaflets67, 68. Moreover, increases in cholesterol have been also reported in cases of fetal alcohol exposure69. The potentiation of GIRK channel activity by cholesterol could amplify the effects of alcohol, perhaps contributing to a comorbidity of cholesterol and alcohol. With a better understanding of the molecular mechanism underlying the direct activation of GIRK channels by small compounds like ethanol and cholesterol, it should be possible to design new drugs that specifically modulate the activity of GIRK channels through these G protein-independent pathways.
