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

The effects of ethanol on the GABA_A 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 GABA_A 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 GABA_A receptors. In granule cells, the sensitivity to GABA increased from 7 to 11 days in vitro. Furosemide, an antagonist of α6-containing GABA_A 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 α6β3δGABA_A 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 GABA_A 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 GABA_A 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.