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- E J Moody, C S Knauer, R Granja, M Strakhovaua, and P Skolnick.
- Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA.
- Toxicol. Lett. 1998 Nov 23;100-101:209-15.
Abstract1. The intravenous anaesthetic etomidate augments GABA-gated chloride currents (indirect action) and, at higher concentrations, evokes chloride currents in the absence of GABA (direct action). 2. In order to identify amino acid residues essential for these actions, site directed mutagenesis was performed on the beta3 subunit. 3. Mutation of an asparagine to a serine residue at position 290 dramatically reduced both etomidate-induced chloride currents and its ability to enhance [3H]flunitrazepam binding in HEK293 cells expressing alpha1beta3gamma2 recombinant GABA(A) receptors. 4. In contrast, the indirect effect of etomidate was retained, though its potency was reduced. 5. These findings indicate that there are distinct requirements for these dual actions of etomidate at GABA(A) receptors.
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