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) 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.
Lambert
Sachar
S
Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Arras
Margarete
M
Vogt
Kaspar E
KE
Rudolph
Uwe
U
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006221:Halothane / Q000494:pharmacology; D006614:Hindlimb; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D012021:Reflex, Abnormal / Q000187:drug effects
D018685:Anesthetics, Inhalation; D021122:Protein Subunits; D011963:Receptors, GABA-A; D007530:Isoflurane; D006221:Halothane