PT  - JOURNAL ARTICLE
AU  - Gerhard Hapfelmeier
AU  - Rainer Haseneder
AU  - Eberhard Kochs
AU  - Michaela Beyerle
AU  - Walter Zieglgänsberger
TI  - Coadministered Nitrous Oxide Enhances the Effect of Isoflurane on GABAergic Transmission by an Increase in Open-Channel Block
DP  - 2001 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 201--208
VI  - 298
IP  - 1
4099  - http://jpet.aspetjournals.org/content/298/1/201.short
4100  - http://jpet.aspetjournals.org/content/298/1/201.full
SO  - J Pharmacol Exp Ther2001 Jul 01; 298
AB  - Clinically relevant concentrations of isoflurane (ISO) and nitrous oxide (N2O) enhance chloride currents induced by activating γ-aminobutyric acidA receptors (GABAAR). Channel blocking by ISO overcomes the enhancing effect at higher concentrations. In this study, the effect of coadministered ISO and N2O on responses evoked by GABA in transfected human embryonic kidney 293 cells carrying α1β2γ2L GABAAR was investigated. Patch-clamp recordings from these cells were performed in the whole cell mode. A piezo-driven “liquid filament” drug application system was used to apply solutions of GABA, ISO, and N2O. Increasing the concentration of ISO in steps from 0.15 to 1.2 mM resulted in a bell-shaped concentration-response curve for GABA-induced currents. The maximum increase in current (1.51 ± 0.14-fold) was seen at 0.45 mM ISO (about 1 minimum alveolar concentration, EC50). N2O (29.2 mM) increased GABA-evoked currents 1.54 ± 0.10-fold. The enhancing effects of ISO and N2O on the GABAergic response were not additive. However, a transient current, associated with the rapid withdrawal of ISO from the receptor, was markedly increased by N2O. Such rebound currents probably reflect the transition from a “channel-blocked” to a “reopened” state. An open-channel block at ligand-gated receptors can prolong postsynaptic currents. Thus, we conclude that coadministered N2O could increase the enhancing effect of ISO on the GABAergic transmission by an increase in open-channel block at the GABAAR. The American Society for Pharmacology and Experimental Therapeutics