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.
Lewohl
J M
JM
Waggoner Center for Alcohol and Addiction Research and Section on Neurobiology, University of Texas at Austin, Austin, Texas 78712, USA. lewohlj@mail.utexas.edu
Wilson
W R
WR
Mayfield
R D
RD
Brozowski
S J
SJ
Morrisett
R A
RA
Harris
R A
RA
D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials; D009865:Oocytes / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014982:Xenopus laevis
D000438:Alcohols; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; C086989:KCNJ1 protein, human; C510692:Kcnj1 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D018080:Receptors, GABA-B; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D000431:Ethanol; D011494:Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins; D011188:Potassium; D002118:Calcium