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.