TY - JOUR T1 - Etomidate Effects on Desensitization and Deactivation of <em>α</em>4<em>β</em>3<em>δ</em> GABA<sub>A</sub> Receptors Inducibly Expressed in HEK293 TetR Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 100 LP - 105 DO - 10.1124/jpet.118.252403 VL - 368 IS - 1 AU - Yiwei Liao AU - Xiang Liu AU - Youssef Jounaidi AU - Stuart A. Forman AU - Hua-Jun Feng Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/368/1/100.abstract N2 - Central α4βδ receptors are the most abundant isoform of δ subunit–containing extrasynaptic GABAA receptors that mediate tonic inhibition. Although the amplitude of GABA-activated currents through α4βδ receptors is modulated by multiple general anesthetics, the effects of general anesthetics on desensitization and deactivation of α4βδ receptors remain unknown. In the current study, we investigated the effect of etomidate, a potent general anesthetic, on the kinetics and the pseudo steady-state current amplitude of α4β3δ receptors inducibly expressed in human embryonic kidney 293 TetR cells. Etomidate directly activates α4β3δ receptors in a concentration-dependent manner. Etomidate at a clinically relevant concentration (3.2 μM) enhances maximal response without altering the EC50 of GABA concentration response. Etomidate also increases the extent of desensitization and prolongs the deactivation of α4β3δ receptors in the presence of maximally activating concentrations of GABA (1 mM). To mimic the modulatory effect of etomidate on tonic currents, long pulses (30–60 seconds) of a low GABA concentration (1 μM) were applied to activate α4β3δ receptors in the absence and presence of etomidate. Although etomidate increases the desensitization of α4β3δ receptors, the pseudo steady-state current amplitude at 1 μM GABA is augmented by etomidate. Our data demonstrate that etomidate enhances the pseudo steady-state current of α4β3δ receptors evoked by a GABA concentration comparable to an ambient GABA level, suggesting that α4β3δ receptors may mediate etomidate’s anesthetic effect in the brain. ER -