Xenon reduces N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission in the amygdala.
BACKGROUND
The neuronal and molecular targets of the inhalational general anesthetic xenon are a matter of debate. The current knowledge is largely based on studies using neurons in culture or heterologous expression systems. In the current study, the authors evaluated for the first time the effect of xenon on synaptic transmission in the basolateral amygdala in an in vitro brain slice preparation of the mouse.


METHODS
A patch clamp technique was used to evaluate the effects of xenon on N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs), as well as on gamma-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents. The currents were either evoked upon electrical stimulation (NMDA-eEPSCs, AMPA-eEPSCs) or upon focal, laser-guided photolysis of caged l-glutamate (p-NMDA-Cs, p-AMPA-Cs). In addition, the authors investigated the effects of xenon on miniature EPSCs.


RESULTS
Xenon reversibly reduced basal synaptic transmission but had no effect on gamma-aminobutyric acid type A receptor-mediated inhibitory synaptic transmission. Xenon concentration-dependently diminished NMDA-eEPSCs and p-NMDA-Cs to the same amount. Likewise, xenon-induced reduction of AMPA-eEPSCs and p-AMPA-Cs did not differ. Xenon did not affect the frequency of miniature EPSCs but reduced their amplitude.


CONCLUSIONS
In the current study, xenon considerably depressed NMDA and AMPA receptor-mediated synaptic transmission in the basolateral amygdala without affecting inhibitory synaptic transmission. The results provide evidence that the effects of xenon on NMDA- and AMPA-EPSCs are primarily mediated via postsynaptic mechanisms.
Haseneder
Rainer
R
Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse22, D-81675 Munich, Germany. haseneder@mpipsykl.mpg.de
Kratzer
Stephan
S
Kochs
Eberhard
E
Eckle
Veit-Simon
VS
Zieglgänsberger
Walter
W
Rammes
Gerhard
G
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014978:Xenon / Q000494:pharmacology*
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon