General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA sub(A) receptor beta 3 subunit

General anesthetics are widely used in clinical practice. In vitro, amino acid residues have been identified within gamma -aminobutyric acid type A (GABA sub(A)) receptor subunits, which are critical for modulating general anesthetic actions; however, the functional relevance of these target sites i...

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Published in:The FASEB journal 2003-02, Vol.17 (2), p.250-252
Main Authors: Jurd, Rachel, Arras, Margarete, Lambert, Sachar, Drexler, Berthold, Siegwart, Roberta, Crestani, Florence, Zaugg, Michael, Vogt, Kaspar E, Ledermann, Birgit, Antkowiak, Bernd, Rudolph, Uwe
Format: Article
Language:English
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Summary:General anesthetics are widely used in clinical practice. In vitro, amino acid residues have been identified within gamma -aminobutyric acid type A (GABA sub(A)) receptor subunits, which are critical for modulating general anesthetic actions; however, the functional relevance of these target sites in mediating essential components of the general anesthetic state in vivo, like immobility and hypnosis, is unknown at this time. Using gene targeting technology, we generated mice harboring a point mutation at one of these identified sites (N265M) located in the second transmembrane region of the beta 3 subunit of the GABA sub(A) receptor. In these mice, behavioral responses to a variety of intravenous (i.v.) and volatile anesthetics were assessed, with the aim of demonstrating whether this residue (N265) within the GABA sub(A) receptor beta 3 subunit is a critical target site mediating general anesthetic responses in vivo.
ISSN:0892-6638
DOI:10.1096/fj.02-0611fje