| First Author | Abramian AM | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 19 | Pages | 7132-7 |
| PubMed ID | 24778259 | Mgi Jnum | J:211067 |
| Mgi Id | MGI:5573090 | Doi | 10.1073/pnas.1403285111 |
| Citation | Abramian AM, et al. (2014) Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci U S A 111(19):7132-7 |
| abstractText | Neurosteroids are synthesized within the brain and act as endogenous anxiolytic, anticonvulsant, hypnotic, and sedative agents, actions that are principally mediated via their ability to potentiate phasic and tonic inhibitory neurotransmission mediated by gamma-aminobutyric acid type A receptors (GABAARs). Although neurosteroids are accepted allosteric modulators of GABAARs, here we reveal they exert sustained effects on GABAergic inhibition by selectively enhancing the trafficking of GABAARs that mediate tonic inhibition. We demonstrate that neurosteroids potentiate the protein kinase C-dependent phosphorylation of S443 within alpha4 subunits, a component of GABAAR subtypes that mediate tonic inhibition in many brain regions. This process enhances insertion of alpha4 subunit-containing GABAAR subtypes into the membrane, resulting in a selective and sustained elevation in the efficacy of tonic inhibition. Therefore, the ability of neurosteroids to modulate the phosphorylation and membrane insertion of alpha4 subunit-containing GABAARs may underlie the profound effects these endogenous signaling molecules have on neuronal excitability and behavior. |
