Kobayashi T, Ikeda K, Kojima H, Niki H, Yano R, Yoshioka T, Kumanishi T
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, Niigata 951-8585, Japan.
Nat Neurosci. 1999 Dec;2(12):1091-7. doi: 10.1038/16019.
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.
乙醇会影响大脑和外周器官的多种功能。我们在此表明，乙醇可开启G蛋白激活的内向整流钾离子（GIRK）通道，这对神经元兴奋性和心率的抑制性调节具有重要意义。在药理学相关浓度下，乙醇可激活脑型GIRK1/2通道和心脏型GIRK1/4通道，且无需与G蛋白或第二信使相互作用。此外，在GIRK2通道中存在错义突变的韦弗突变小鼠表现出乙醇诱导的镇痛作用丧失。这些结果表明，大脑和心脏中的GIRK通道是乙醇的重要靶点。
