Nature Neuroscience
2, 1091 - 1097 (1999)
doi:10.1038/16019
Ethanol opens G-protein-activated inwardly rectifying K+
channelsToru Kobayashi1, 2, Kazutaka Ikeda3, 4, Hiroshi Kojima5, 6, Hiroaki Niki3, Ryoji Yano4, Tohru Yoshioka5, 6
& Toshiro Kumanishi11
Department of Molecular Neuropathology, Brain Research
Institute, Niigata University, 1-757 Asahimachi, Niigata,
Niigata 951-8585, Japan
2
Department of Psychiatry, Niigata University School
of Medicine, Asahimachi, Niigata, Niigata
951-8510, Japan
3
Laboratory for Neurobiology of Emotion, Brain Science
Institute, RIKEN, Hirosawa, Wako, Saitama
351-0198, Japan
4
Laboratory for Cellular Information Processing, Brain
Science Institute, RIKEN, Hirosawa, Wako, Saitama
351-0198, Japan
5
Advanced Research Institute for Science and Engineering,
Waseda University, Shinjuku, Tokyo 169-8555,
Japan
6
Department of Molecular Neurobiology, School of Human
Sciences, Waseda University, Tokorozawa Saitama 359-1164
, Japan
Correspondence should be addressed to Toru Kobayashi kobato@bri.niigata-u.ac.jpEthanol 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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