Gamma-aminobutyric acid type A receptor beta 2 subunit mediates the hypothermic effect of etomidate in mice.
BACKGROUND
The authors have previously described that the gamma-aminobutyric acid type A (GABAA) receptor beta 2N265S 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 GABAA receptor beta 2N265S mutant mice and wild-type controls.


RESULTS
beta 2N265S mutant mice have a reduced hypothermic response to anesthetic doses of etomidate compared with wild-type 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 GABAA receptor beta 2 subunit mediates a significant proportion of the hypothermic effects of etomidate. As the beta 2 subunit mediates postrecovery ataxia and sedation, anesthetic agents that do not have in vivo potency at beta 2 subunit-containing receptors offer the potential for surgical anesthesia with improved recovery characteristics.
Cirone
Jennifer
J
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
Rosahl
Thomas W
TW
Reynolds
David S
DS
Newman
Richard J
RJ
O'Meara
Gillian F
GF
Hutson
Peter H
PH
Wafford
Keith A
KA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000235:genetics; D005045:Etomidate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007035:Hypothermia / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology*; D018079:Receptors, GABA / Q000235:genetics / Q000502:physiology*; D011963:Receptors, GABA-A; D013997:Time Factors
C470436:Gabrb2 protein, mouse; D021122:Protein Subunits; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005045:Etomidate