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• W2129349320 abstract "Interactions between neurosteroids and GABA receptors have attracted particular attention in the supraoptic nucleus (SON). Although GABA A receptors (GABA A R) mediate a sustained tonic inhibitory current (I tonic ), as well as conventional phasic inhibitory postsynaptic currents (IPSCs, I phasic ) in the SON, whether the steroid modulation on I tonic is present in SON magnocelluar neurosecretory cells (MNCs) is unknown. Here, we addressed this question and gained insights into the potential molecular configuration of GABA A receptors mediating I tonic and conferring its neurosteroids sensitivity in SON MNCs. 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (1 μM), a relatively selective extrasynaptic GABA A R agonist, facilitated I tonic without affecting the main characteristics of IPSCs, while DS-2, a relatively selective modulator of GABA A R δ-subunits, caused minimal changes in I tonic of SON MNCs. l-655,708, a relatively selective GABA A R α 5 -subunit inverse agonist, blocked ∼35% of the total I tonic both under basal and elevated ambient GABA concentration (3 μM). Facilitation of I tonic by benzodiazepines further supported the role of GABA A R γ 2 -subunit in I tonic of SON MNCs. Quantitative RT-PCR analysis showed much lesser expression of GABA A R δ-subunit than the α 5 or γ 2 -subunit in the SON. Allopregnanolone and 3α,5α-tetrahydrodeoxycorticosterone increased both I tonic and I phasic in SON MNCs, respectively, although more than 90% of the current increase was mediated by I tonic during the neurosteroid facilitation. Finally, l-655,708 attenuated the neurosteroid facilitation of I tonic but not of I phasic . Altogether, our results suggest that I tonic , mediated mainly by benzodiazepine-sensitive GABA A Rs containing α 5 -, β-, and γ 2 -, and to a lesser extent, δ-subunits, is a potential target of neurosteroid modulation in SON neurons." @default.
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• W2129349320 date "2011-06-01" @default.
• W2129349320 modified "2023-10-17" @default.
• W2129349320 title "Neurosteroid modulation of benzodiazepine-sensitive GABA_A tonic inhibition in supraoptic magnocellular neurons" @default.
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• W2129349320 doi "https://doi.org/10.1152/ajpregu.00627.2010" @default.
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• W2129349320 hasPublicationYear "2011" @default.
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