Modulation of GABAA receptors by benzodiazepines and barbiturates is autonomous of PKC activation

Emmanuel Ghansah, David S. Weiss

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Previous studies have suggested that activation of calcium-phospholipid-dependent protein kinase (PKC) enhances benzodiazepine (BZD)- and pentobarbital (PB)- mediated potentiation of α1β1γ2 GABAA receptors (GABAA-Rs). To delineate the underlying mechanism(s), voltage-clamp recordings were performed on recombinant α1β1γ2 GABAA receptors functionally expressed in Xenopus laevis oocytes. GABAA-Rs were tested for their sensitivity to diazepam and PB before and after incubation in phorbol 12-myristate 13-acetate (PMA). PMA (25 nM) significantly attenuated the GABAA current (p<0.05, n=12-19) up to 90%. PMA treatment, however, did not alter the sensitivity to diazepam or pentobarbital. Similar results were obatined with recombinant α1β2γ2 GABA receptors. These data suggest that PKC activation does not alter the allosteric modulation of GABAA-Rs by benzodiazepines and barbiturates and is consistent with the observation from other studies in oocytes that PMA decreases the amplitude of the GABA-activated currents via receptor internalization rather than modification of receptor kinetics.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalNeuropharmacology
Volume40
Issue number3
DOIs
StatePublished - Feb 21 2001
Externally publishedYes

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Keywords

  • Affinity
  • Diazepam
  • PMA
  • Pentobarbital
  • Phosphorylation
  • Voltage-clamp

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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