Basis of variable sensitivities of GABA(A) receptors to ethanol

Takashi Mori, Gary L. Aistrup, Kiyonobu Nishikawa, William Marszalec, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: The GABA(A) system is believed to be one of the crucial target sites for ethanol. However, in the literature, data using various preparations yielded controversial conclusions regarding the ethanol potency to modulate the activity of GABA(A) receptors. We have previously shown that the potency of n-alcohols to potentiate GABA-induced currents is correlated with their carbon chain length. This correlation was further compared among four cell types in an attempt to explain the variable potencies of ethanol to potentiate GABA responses. Methods: Whole-cell patch clamp experiments were performed to determine and compare the potencies of n-alcohols in potentiating GABA-induced currents in rat dorsal root ganglion (DRG) neurons, human embryonic kidney cells expressing the rat α1β2γ2S or α1β2γ2L subunits, and rat cortical neurons. Results: The GABA(A) receptors of the four cell types tested were all sensitive to n-alcohols, albeit with different potencies and efficacies. The effective concentration to increase GABA-induced currents to 125% of control (EC125) was correlated with the carbon chain length of n-alcohols, but slopes for this relationship are different among DRG neurons, the α1β2γ2S, and α1β2γ2L subunits. Thus, the potencies of lower alcohols such as ethanol differed among these cell types although higher alcohols such as n-octanol were almost equally potent. In cortical neurons, however, the relationship was shifted in the direction of longer carbon chains, indicating that their sensitivity was lower than those of the other three cell types. The ethanol EC125 values as obtained by experiments or those by extrapolation (in parenthesis) from the EC125- carbon chain length relationship were: 169 (103) mM for DRG neurons, 501 (333) mM for the α1β2γ2L subunits, 781 (674) mM for the α1β2γ2S subunits, and (1897) mM for cortical neurons. Conclusions: It was concluded that the GABA(A) receptors of these four cell types were basically sensitive to n-alcohols including ethanol but the sensitivity curve was shifted to the lower side in the order of decreasing sensitivity of DRG neurons > α1β2γ2L > α1/β2γ2S > cortical neurons.

Original languageEnglish (US)
Pages (from-to)965-971
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number7
DOIs
StatePublished - Jul 2000

Keywords

  • Alcohol
  • Channel Modulation
  • Ethanol
  • GABA(A) Receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Basis of variable sensitivities of GABA(A) receptors to ethanol'. Together they form a unique fingerprint.

Cite this