Does ethanol activate G-protein coupled inwardly rectifying K+ channels?
G-protein coupled inwardly rectifying K+ (GIRK) channels have been reported to be targets of ethanol actions. We investigated if ethanol affects native GIRK channels in rat brain tissues at clinically relevant concentrations using brain slices containing the ventrolateral periaqueductal gray (PAG), an area related to pain regulation. Ethanol did not affect the membrane current elicited by hyperpolarization ramps at concentrations up to 150 mM. However, at 200-300 mM, which is above the lethal level, it activated a barium-sensitive GIRK current in 30-57% of neurons. In neurons unresponsive to ethanol, baclofen, the mu-opioid or nociceptin successfully activated GIRK channels. It is suggested that GIRK channels of the ventrolateral PAG are unlikely to be targets of the analgesic action of ethanol.
Chiou
Lih-Chu
LC
Department of Pharmacology, Medical College, National Taiwan University, Taipei.
Chuang
Kuang-Chieh
KC
Fan
Shu-Huai
SH
How
Cheng-Hung
CH
Chen
Jen-Kun
JK
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D004553:Electric Conductivity; D000431:Ethanol / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000166:cytology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000097629:Nociceptin
D001418:Baclofen; D017609:Barium Compounds; D002492:Central Nervous System Depressants; D002712:Chlorides; D000431:Ethanol; D018755:GABA Agonists; D019204:GTP-Binding Proteins; D018847:Opioid Peptides; D024661:Potassium Channels, Inwardly Rectifying; D000097629:Nociceptin; C024986:barium chloride