Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alcohols / chemistry
-
Alcohols / pharmacology
-
Animals
-
Brain
-
Ethanol / pharmacology*
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors
-
Heterotrimeric GTP-Binding Proteins / metabolism*
-
Ion Channel Gating / drug effects*
-
Mice
-
Mice, Inbred C3H
-
Mice, Mutant Strains
-
Motor Activity / drug effects
-
Mutation, Missense / genetics
-
Myocardium
-
Oocytes / metabolism
-
Pain Measurement / drug effects
-
Patch-Clamp Techniques
-
Potassium / metabolism
-
Potassium / pharmacology
-
Potassium Channels / genetics
-
Potassium Channels / metabolism*
-
Potassium Channels, Inwardly Rectifying*
-
Receptors, Opioid, mu / agonists
-
Receptors, Opioid, mu / genetics
-
Receptors, Opioid, mu / metabolism
-
Second Messenger Systems / drug effects
-
Xenopus laevis
Substances
-
Alcohols
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Potassium Channels
-
Potassium Channels, Inwardly Rectifying
-
Receptors, Opioid, mu
-
Ethanol
-
Heterotrimeric GTP-Binding Proteins
-
Potassium
Associated data
-
GENBANK/AB019560
-
GENBANK/AB024304