Ethanol opens G-protein-activated inwardly rectifying K+ channels.
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.
Kobayashi
T
T
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, Niigata 951-8585, Japan. kobato@bri.niigata-u.ac.jp
Ikeda
K
K
Kojima
H
H
Niki
H
H
Yano
R
R
Yoshioka
T
T
Kumanishi
T
T
D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001921:Brain; D000431:Ethanol / Q000494:pharmacology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects; D020125:Mutation, Missense / Q000235:genetics; D009206:Myocardium; D009865:Oocytes / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D014982:Xenopus laevis
D000438:Alcohols; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017450:Receptors, Opioid, mu; D000431:Ethanol; D020962:Heterotrimeric GTP-Binding Proteins; D011188:Potassium