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.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience