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- W1954401748 abstract "The intravenous general anesthetic 2,6-diisopropylphenol (propofol) potentiates GABAA receptor function, but the precise mechanisms and specificity of this action are still unclear. To study the influence of receptor subunit composition on the action of propofol, 18 different combinations of cloned cDNAs coding for human brain subunit isoforms of the GABAA receptor, as well as mRNAs from mouse brain, were expressed in Xenopus oocytes, and effects of this anesthetic were investigated by the voltage-clamp technique. We found that low concentrations (1-10 microM) of propofol dramatically potentiated GABA-evoked Cl- currents in all GABAA receptor constructs tested. This action did not require specific subunits but was correlated inversely with the GABA sensitivity of each receptor construct. Larger concentrations (10-25 microM) of propofol produced direct activation of Cl- currents, and this action was dependent on the expression of the beta-subunit of the GABAA receptor and did not correlate with the GABA sensitivity of the receptors. These results suggest that propofol exerts a dual effect on GABAA receptors: a positive modulation of the GABA-mediated action on GABAA receptors that is not influenced by the receptor subunit composition, and a specific interaction with the beta-subunit that directly activates the GABAA receptor-coupled Cl- channel." @default.
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- W1954401748 date "1995-07-01" @default.
- W1954401748 modified "2023-10-18" @default.
- W1954401748 title "Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits." @default.
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