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• W2974970743 abstract "The synaptic α1β2γ2 GABAA receptor is activated phasically by presynaptically released GABA. The receptor is considered to be inactive between synaptic events when exposed to ambient GABA because of its low resting affinity to the transmitter. We tested the hypothesis that a combination of physiological and/or clinical positive allosteric modulators of the GABAA receptor with ambient GABA generates measurable steady-state activity. Recombinant α1β2γ2L GABAA receptors were expressed in Xenopus oocytes and activated by combinations of low concentrations of orthosteric (GABA, taurine) and allosteric (the steroid allopregnanolone, the anesthetic propofol) agonists, in the absence and presence of the inhibitory steroid pregnenolone sulfate. Steady-state activity was analyzed using the three-state cyclic Resting-Active-Desensitized model. We estimate that the steady-state open probability of the synaptic α1β2γ2L GABAA receptor in the presence of ambient GABA (1 μmol/L), taurine (10 μmol/L), and physiological levels of allopregnanolone (0.01 μmol/L) and pregnenolone sulfate (0.1 μmol/L) is 0.008. Coapplication of a clinical concentration of propofol (1 μmol/L) increases the steady-state open probability to 0.03. Comparison of total charge transfer for phasic and tonic activity indicates that steady-state activity can contribute strongly (~20 to >99%) to integrated activity from the synaptic GABAA receptor." @default.
• W2974970743 created "2019-10-03" @default.
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• W2974970743 date "2019-09-01" @default.
• W2974970743 modified "2023-10-15" @default.
• W2974970743 title "Steady‐state activation and modulation of the synaptic‐type <i>α</i> 1 <i>β</i> 2 <i>γ</i> 2L GABA _A receptor by combinations of physiological and clinical ligands" @default.
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• W2974970743 doi "https://doi.org/10.14814/phy2.14230" @default.
• W2974970743 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6757177" @default.
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• W2974970743 hasPublicationYear "2019" @default.
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