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