Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors.
We investigated the interactions between recombinant gamma-aminobutyric acid receptor complex (GABA(A)R) and nitrous oxide (N(2)O) 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 N(2)O and Xe on GABA-induced currents. A piezo-driven "liquid filament switch" was used for fast application. Both N(2)O (100%, 29.2 mM) and Xe (100%, 3.9 mM) reversibly increased GABA-induced currents through the alpha(1)ss(2)gamma(2L) and the alpha(1)beta(2) GABA(A)R channels. The potentiating effect of N(2)O or Xe on peak currents was prominent at small GABA concentrations (10(-7) to 10(-5) M). The addition of N(2)O or Xe increased the efficacy of GABA (10(-7) to 10(-3) M). Both N(2)O and Xe significantly decreased the risetime((10%-90%)) of the currents elicited by small GABA concentrations. At the concentrations used, neither N(2)O nor Xe had an intrinsic effect. We conclude that, similar to other anesthetics, both N(2)O and Xe increase the efficacy of GABA at the GABA(A)R and enhance inhibitory GABAergic synaptic transmission.
Hapfelmeier
G
G
Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, München, Germany. hapfelmeier@mpipsykl.mpg.de
Zieglgänsberger
W
W
Haseneder
R
R
Schneck
H
H
Kochs
E
E
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000378:metabolism; D009609:Nitrous Oxide / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014978:Xenon / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D018685:Anesthetics, Inhalation; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D014978:Xenon; D005680:gamma-Aminobutyric Acid; D009609:Nitrous Oxide