Modulation of recombinant α6β2γ2 GABAA receptors by neuroactive steroids

Charlotte Hauser*, Dominique Chesnoy-Marchais, Paul Robel, Etienne E. Baulieu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The sensitivity of the recombinant α6β2γ2 GABAA receptor expressed in HEK 293 cells to neuroactive steroids was studied. The steroids 3α-hydroxy-5α-pregnan-20-one (3α-OH-DHP), pregnenolone sulfate and 3α-OH-DHP sulfate have different modulatory effects on [3H]muscimol or [3H]Ro15-4513 binding to the α6β2γ2 than to the α1β2γ2 receptor. Binding of both radioactive ligands to the α6β2γ2 receptor was maximally potentiated with each steroid used (10 nM) and decreased with further increases in steroid concentration. Using whole-cell recording, the GABA response of clusters of transfected HEK 293 cells was strongly potentiated by 3 or 10 nM 3α-OH-DHP. In contrast, this response was reduced by 100 nM 3α-OH-DHP. This latter effect appears to be related to the acceleration of the GABA response desensitization, observed in isolated cells. 3α-OH-DHP (10 or 100 nM) was able to activate a response in the absence of GABA. It is proposed that the interaction of neuroactive steroids with the α6β2γ2 receptor involves at least two distinct binding sites. One of them might be located close to the GABA binding site.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume289
Issue number2
DOIs
StatePublished - Apr 28 1995

Keywords

  • (Ligand binding modulation)
  • GABA receptor, recombinant
  • Neuroactive steroids
  • Patch clamp

ASJC Scopus subject areas

  • Pharmacology

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