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• W1601574502 startingPage "307" @default.
• W1601574502 abstract "Central GABA(A) receptors mediate GABAergic phasic and tonic inhibition. While synaptic αβγ GABA(A) receptors primarily mediate phasic inhibition, extrasynaptic αβδ receptors play an important role in mediating tonic inhibition. Etomidate is a general anesthetic that produces its effects by enhancing GABA(A) receptor activity. We previously showed that etomidate modulates the gating of oocyte-expressed αβγ and αβδ receptors with similar overall allosteric impact, but different pharmacological patterns. In αβγ receptors, etomidate enhances apparent GABA sensitivity (reduces GABA EC50), modestly increases maximal GABA efficacy, and slows current deactivation without affecting desensitization (Zhong et al., 2008). In αβδ receptors characterized by low GABA efficacy, etomidate dramatically increases responses to both low and maximal GABA. The effects of etomidate on desensitization and deactivation of αβδ receptors are unknown. To investigate the kinetic effects of etomidate on α1β3δ receptors of defined subunit arrangement, we expressed concatenated trimer (β3-α1-δ) and dimer (β3-α1) GABA(A) receptor subunit assemblies in human embryonic kidney (HEK)293T cells and recorded whole-cell voltage-clamp currents during rapid external solution exchanges. As expected, etomidate substantially increased maximal GABA-induced currents and prolonged deactivation. Moreover, desensitization was significantly decreased by etomidate. During prolonged GABA applications, etomidate enhanced steady-state currents more than peak currents. Thus, etomidate enhances tonic GABAergic inhibition through extrasynaptic αβδ receptors by both augmenting gating and reducing desensitization." @default.
• W1601574502 created "2016-06-24" @default.
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• W1601574502 date "2015-08-01" @default.
• W1601574502 modified "2023-09-30" @default.
• W1601574502 title "Etomidate uniquely modulates the desensitization of recombinant α1β3δ GABAA receptors" @default.
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• W1601574502 doi "https://doi.org/10.1016/j.neuroscience.2015.05.051" @default.
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