Selective effects of alcohols on γ-aminobutyric acid A receptor subunits expressed in human embryonic kidney cells

W. Marszalec, Y. Kurata, B. J. Hamilton, D. B. Carter, T. Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Several previous studies implicated α6 and γ(2L) subunits as potential determinants of γ-aminobutyric acid A (GABA(A)) receptor channel sensitivity to alcohol modulation. The effects of ethanol and n-octanol were studied on GABA-induced currents in human embryonic kidney cells transfected to express one of three different GABA(A) receptor channel subunit combinations: α1β2γ(2S), α6β2γ(2S) or α0β2γ(2L). No increase in the current amplitude of any subunit combination was observed after the coapplication of GABA and physiological concentrations (10-100 mM) of ethanol. By contrast, the coapplication of GABA and 100 μM octanol increased the current amplitude by 50% to 100% in all three subunit combinations. Octanol produced a shift of the current dose-response curve toward lower concentrations of GABA. Ethanol was effective in increasing the rate of desensitization produced by higher concentrations of GABA in the α6β2γ(2S) cells but not the α1β2γ(2S) combination. This ethanol-induced modification of desensitization was not altered by the presence of the protein kinase inhibitor 1-(5- isoquinolinesulfonyl)-2-methylpiperazine (H-7). These experiments indicate that the presence of α6 or γ(2L) subunits, in itself, does not result in the potentiation of GABA-induced currents by ethanol, as described in some reports. However, the presence of either the α6 or α1 subunit may determine whether the desensitization rate of the GABA(A) current is affected by the alcohol.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number1
StatePublished - 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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