N-methyl-D-aspartic acid receptor activation downregulates expression of δ subunit-containing GABAA receptors in cultured hippocampal neurons.

ABSTRACT: Neurosteroids are endogenous allosteric modulators of GABAA receptors (GABARs), and they enhance GABAR-mediated inhibition. However, GABARs expressed on hippocampal dentate granule neurons of epileptic animals are modified such that their neurosteroid sensitivity is reduced and δ subunit expression is diminished. We explored the molecular mechanisms triggering this GABAR plasticity. In the cultured hippocampal neurons, treatment with N-methyl-D-aspartic acid (NMDA) (10 μM) for 48 hours reduced the surface expression of δ and α4 subunits but did not increase the expression of γ2 subunits. The tonic current recorded from neurons in NMDA-treated cultures was reduced, and its neurosteroid modulation was also diminished. In contrast, synaptic inhibition and its modulation by neurosteroids were

SUBMITTER: Joshi S 

PROVIDER: S-EPMC3684822 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature