Enflurane actions on spinal cords from mice that lack the beta3 subunit of the GABA(A) receptor.
BACKGROUND
Gamma-aminobutyric acid type A (GABA(A)) receptors are considered important in mediating anesthetic actions. Mice lacking the beta3 subunit of this receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC) than wild types (+/+). MAC is predominantly determined in spinal cord.


METHODS
The authors measured three population-evoked responses in whole spinal cords, namely, the excitatory postsynaptic potential (pEPSP), the slow ventral root potential (sVRP), and the dorsal root potential. Synaptic and glutamate-evoked currents from motor neurons in spinal cord slices were also measured.


RESULTS
Sensitivity of evoked responses to enflurane did not differ between +/+ and -/- cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05) attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate-evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords, but the interactions between strychnine and enflurane did not differ between -/- and +/+ cords.


CONCLUSIONS
Similar enflurane sensitivity in spinal cords from -/- and +/+ mice was coupled with a decreased role for GABA(A) receptors in mediating the actions of enflurane in the former. This finding implies that other anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor-mediated inhibition was found in -/- cords, but the glycine receptor does not appear to be a substitute anesthetic target. This mutation thus led to a quantitative change in the molecular basis for anesthetic depression of spinal neurotransmission in a fashion not predicted by the mutation itself. The results argue against an immutable dominant role for GABA(A) receptors in mediating spinal contributions to MAC.
Wong
S M
SM
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
Cheng
G
G
Homanics
G E
GE
Kendig
J J
JJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004737:Enflurane / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics*; D018009:Receptors, Glycine / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects; D017384:Sequence Deletion; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D017661:Receptors, Presynaptic; D013779:Tetrodotoxin; D004737:Enflurane