Ethanol affects many functions of the brain and peripheral organs. Here we show that ethanol opens G-protein-activated, inwardly rectifying K+ (GIRK) channels, which has important implications for inhibitory regulation of neuronal excitability and heart rate. At pharmacologically relevant concentrations, ethanol activated both brain-type GIRK1/2 and cardiac-type GIRK1/4 channels without interaction with G proteins or second messengers. Moreover, weaver mutant mice, which have a missense mutation in the GIRK2 channel, showed a loss of ethanol-induced analgesia. These results suggest that the GIRK channels in the brain and heart are important target sites for ethanol.
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We thank J. G. Connolly and R. Kado for critical reading of the manuscript, K. Sakimura, K. Shimoji, Y. Ishihara, T. Someya and K. Baba for their cooperation and H. Kishida, N. Yamazaki, T. Ichikawa and K. Kobayashi for their assistance. This work was supported by a research grant from the Ministry of Education, Science, Sports and Culture of Japan, by the Cooperative Research Program of the RIKEN Brain Science Institute and in part by Research for the Future Program from the Japan Society for the Promotion of Science.
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Kobayashi, T., Ikeda, K., Kojima, H. et al. Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nat Neurosci 2, 1091–1097 (1999). https://doi.org/10.1038/16019