Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABAA receptors

We investigated the interactions between recombinant gamma-aminobutyric acid receptor complex (GABA(A)R) and nitrous oxide (N2O) or xenon (Xe). Human embryonic kidney cells (HEK 293) were transfected with rat cDNA for alpha (1)beta (2)gamma (2L) or for alpha (1)beta (2) recombinant GABA(A)R subunits. Patch clamp techniques were used in the whole-cell mode to evaluate the effect of N2O and Xe on GABA-induced currents. A piezo-driven "liquid filament switch" was used for fast application. Both N2O (100%, 29.2 mM) and Xe (100%, 3.9 mM) reversibly increased GABA-induced currents through the alpha (1)beta (2)gamma (2L) and the alpha (1)beta (2) GABA(A)R channels. The potentiating effect of N2O or Xe on peak currents was prominent at small GABA concentrations (10(-7) to 10(-5) M). The addition of N2O or Xe increased the efficacy of GABA (10(-7) to 10(-3) M). Both N2O and Xe significantly decreased the risetime((10%-90%)) of the currents elicited by small GABA concentrations. At the concentrations used, neither N2O nor Xe had an intrinsic effect. We conclude that, similar to other anesthetics, both N2O and Xe increase the efficacy of GABA at the GABA(A)R and enhance inhibitory GABAergic synaptic transmission.