Nanomolar allopregnanolone potentiates rat cerebellar GABAA receptors

László Fodor, Tímea Bíró, Gábor Maksay

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The ionophore function of γ-aminobutyric acid A (GABAA) receptors was studied by whole-cell patch clamp electrophysiology in primary cultures of rat cerebellar cortex. Chloride currents elicited by 1 μM GABA were potentiated by allopregnanolone with a plateau of high affinity (EC 50 = 14 nM) and a peak of potentiation around 1 μM allopregnanolone. Furosemide (0.1 mM) eliminated the high affinity phase and increased the EC50 to 685 nM. GABAA receptors of rat cerebellar synaptosomal membranes were labelled with [3H] ethynylbicycloorthobenzoate (EBOB). Allopregnanolone displaced [ 3H]EBOB binding with IC50 = 320 nM. The displacing potency of allopregnanolone was strongly enhanced (IC50 = 39 nM) in the presence of 400 nM GABA and 60 nM SR 95531. Nanomolar potentiation by allopregnanolone can be associated with cerebellar GABAA receptors containing α6, β2-3 and δ subunits. This might be suitable for physiological modulation of tonic inhibitory neurotransmission via extrasynaptic GABAA receptors in cerebellar granule cells by neurosteroids.

Original languageEnglish
Pages (from-to)127-130
Number of pages4
JournalNeuroscience Letters
Volume383
Issue number1-2
DOIs
Publication statusPublished - Jul 22 2005

Keywords

  • Allopregnanolone
  • Cerebellar granule cells
  • Displacement of [H]EBOB binding
  • Furosemide
  • αβδ GABA receptors
  • γ-Aminobutyric acid A receptor-ionophore

ASJC Scopus subject areas

  • Neuroscience(all)

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