G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action.
G-protein-coupled inwardly rectifying potassium channels (GIRKs) are important for regulation of synaptic transmission and neuronal firing rates. Because of their key role in brain function, we asked if these potassium channels are targets of alcohol action. Ethanol enhanced function of cerebellar granule cell GIRKs coupled to GABAB receptors. Enhancement of GIRK function by ethanol was studied in detail using Xenopus oocytes expressing homomeric or heteromeric channels. Function of all GIRK channels was enhanced by intoxicating concentrations of ethanol, but other, related inwardly rectifying potassium channels were not affected. GIRK2/IRK1 chimeras and GIRK2 truncation mutants were used to identify a region of 43 amino acids in the carboxyl (C) terminus that is critical for the action of ethanol on these channels.
PubMed ID: 10570485
Article link: Nat Neurosci.
Grant support: AA03527 NIAAA NIH HHS , AA06399 NIAAA NIH HHS , GM47818 NIGMS NIH HHS
Genes referenced: kcnj12 kcnj2 kcnj3 kcnj6