Effects of ethanol on tonic GABA currents in cerebellar granule cells and mammalian cells recombinantly expressing GABAA receptors

Megumi Yamashita, William Marszalec, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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 GABA A 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.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume319
Issue number1
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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