TY - JOUR T1 - Effects of Ethanol on Tonic GABA Currents in Cerebellar Granule Cells and Mammalian Cells Recombinantly Expressing GABA<sub>A</sub> Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 431 LP - 438 DO - 10.1124/jpet.106.106260 VL - 319 IS - 1 AU - Megumi Yamashita AU - William Marszalec AU - Jay Z. Yeh AU - Toshio Narahashi Y1 - 2006/10/01 UR - http://jpet.aspetjournals.org/content/319/1/431.abstract N2 - The effects of ethanol on the GABAA receptors, which are regarded as one of the most important target sites of ethanol, are very controversial, ranging from potentiation to no effect. The δ subunit-containing GABAA receptors expressed in Xenopus oocytes were recently reported to be potently augmented by ethanol. We performed patch-clamp experiments using the cerebellar granule cells and mammalian cells expressing recombinant GABAA receptors. In granule cells, the sensitivity to GABA increased from 7 to 11 days in vitro. Furosemide, an antagonist of α6-containing GABAA receptors, inhibited GABA-induced currents more potently at 11 to 14 days than at 7 days. Ethanol at 30 mM had either no effect or an inhibitory effect on currents induced by low concentrations of GABA in granule cells. On α4β2δ, α6β2δ, or α6β3δGABAA receptors expressed in Chinese hamster ovary cells, ethanol at 10, 30, and 100 mM had either no effect or an inhibitory effect on GABA currents. Ethanol inhibition of GABAA receptor was observed in all of the subunit combinations examined. In contrast, the perforated patch-clamp method to record the GABA currents revealed ethanol effects on the α6β2δ subunits ranging from slight potentiation to slight inhibition. Ethanol seems to exert a dual action on the GABAA receptors and the potentiating action may depend on intracellular milieu. Thus, the differences between the GABAA receptors expressed in mammalian host cells and those in Xenopus oocytes in the response to ethanol might be due to changes in intracellular components under patch-clamp conditions. The American Society for Pharmacology and Experimental Therapeutics ER -