Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptors

The targets which mediate the actions of the volatile general anaesthetic isoflurane are unknown. Based on pharmacological studies using GABA(A) receptor antagonists it has recently been suggested that GABA(A) receptors would not mediate the immobilizing action of isoflurane. Using the beta3(N265M)...

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Bibliographic Details
Published in:European journal of pharmacology 2005-05, Vol.516 (1), p.23-27
Main Authors: Lambert, Sachar, Arras, Margarete, Vogt, Kaspar E, Rudolph, Uwe
Format: Article
Language:English
Subjects:
Anesthetics, Inhalation - pharmacology
Animals
Dose-Response Relationship, Drug
Female
Genotype
Halothane - pharmacology
Hindlimb
Isoflurane - pharmacology
Male
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Mutation, Missense
Protein Subunits - genetics
Protein Subunits - physiology
Receptors, GABA-A - genetics
Receptors, GABA-A - physiology
Reflex, Abnormal - drug effects
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Summary:The targets which mediate the actions of the volatile general anaesthetic isoflurane are unknown. Based on pharmacological studies using GABA(A) receptor antagonists it has recently been suggested that GABA(A) receptors would not mediate the immobilizing action of isoflurane. Using the beta3(N265M) knock-in mouse model we found that the mutant mice were less sensitive to the immobilizing action of isoflurane, indicating a role of beta3-containing GABA(A) receptors in mediating immobility. At high concentrations isoflurane also immobilizes beta3(N265M) mice, indicating that other targets also mediate immobility. Thus, our findings support a multisite model for the immobilizing action of isoflurane.
ISSN:0014-2999