γ-aminobutyric acid type A receptor β2 subunit mediates the hypothermic effect of etomidate in mice

Background The authors have previously described that the gamma-aminobutyric acid type A (GABA(A)) receptor beta2N265S mutation results in a knock-in mouse with reduced sensitivity to etomidate. After recovery from etomidate anesthesia, these mice have improved motor performance and less slow wave sleep. Because most clinically used anesthetics produce hypothermia, the effect of this mutation on core body temperature was investigated. Methods: The effect of etomidate and propofol on core body temperature were measured using radiotelemetry in freely moving GABA(A) receptor beta2N265S mutant mice and wild-type controls. Results: beta2N265S mutant mice have a reduced hypothermic response to anesthetic doses of etomidate compared with wildtype controls and after a transient loss of righting reflex regain normothermia more rapidly compared with wild-type controls. Subanesthetic doses of etomidate produce hypothermia, which was not observed in the mutant mice. Vehicle administration resulted in a stress-induced hyperthermic response in both genotypes. Propofol produced a hypothermic response that was similar in both genotypes. Conclusions: The GABA(A) receptor beta2 subunit mediates a significant proportion of the hypothermic effects of etomidate. As the beta2 subunit mediates postrecovery ataxia and sedation, anesthetic agents that do not have in vivo potency at beta2 subunit-containing receptors offer the potential for surgical anesthesia with improved recovery characteristics.