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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on July 14, 2006; DOI: 10.1124/jpet.106.106260

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*Compound via MeSH
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*ETHANOL
*FUROSEMIDE


Received for publication April 19, 2006.
Revised July 12, 2006.
Accepted for publication July 13, 2006.

Effects of Ethanol on Tonic GABA Currents in Cerebellar Granule Cells and Mammalian Cells Recombinantly Expressing GABAA Receptors

Megumi Yamashita 1, William Marszalec 1, Jay Z. Yeh 1, Toshio Narahashi 1*

1 Northwestern University Medical School

* Address correspondence to: E-mail: narahashi{at}northwestern.edu

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 {delta} 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 days to 11 days in vitro. Furosemide, an antagonist of {alpha}6-containing GABAA receptors, inhibited GABA-induced currents more potently at 11-14 days than that 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 {alpha}4{beta}3{delta}, {alpha}6{beta}2{delta} or {alpha}6{beta}3{delta} GABAA 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 the subunit combinations examined. In contrast, the perforated patch clamp method to record the GABA currents revealed ethanol effects on the {alpha}6{beta}2{delta} subunits ranging from slight potentiation to slight inhibition. Ethanol appears 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.


Key words: Xenopus oocyte, Alcohol, Chinese hamster ovary cell, Furosemide, GABAA receptor, granule cell


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