Depression of Synaptic N-methyl-D-Aspartate Responses by Xenon and Nitrous Oxide

Abstract

In "synapse bouton preparation" of rat hippocampal CA3 neurons, we examined how Xe and N2O modulate N-methyl-D-aspartate (NMDA) receptor-mediated spontaneous and evoked excitatory post-synaptic currents (sEPSCNMDA and eEPSCNMDA) excluded extrasynaptic, glial and other neuronal tonic currents. This preparation is a mechanically isolated single neuron attached with nerve endings (boutons) preserving normal physiological function and promotes the exact evaluation of sEPSCNMDA and eEPSCNMDA These sEPSC and eEPSC are elicited by spontaneous glutamate (Glu) release from many homologous glutamatergic boutons and by focal paired-pulse electric stimulation of a single bouton, respectively. The s/eEPSCAMPA/KA and s/eEPSCNMDA were isolated pharmacologically by their specific antagonists. Thus, independent contributions of pre- and postsynaptic responses be could also quantified. All kinetic properties of s/eEPSCAMPA/KA and s/eEPSCNMDA were detected clearly. The s/eEPSCNMDA showed smaller amplitude, slower rise and 1/e decay time constant (τDecay) than s/eEPSCAMPA/KA Xe (70%) and N2O (70%) significantly decreased the frequency and amplitude without altering the τDecay of sEPSCNMDA They also decreased the amplitude but increased the Rf and PPR without altering the τDecay of the eEPSCNMDA These data show clearly that "synapse bouton preparation" can be an accurate model for evaluating s/eEPSCNMDA Such inhibitory effects of gas anesthetics are primarily due to presynaptic mechanisms. Present results may explain partially the powerful analgesic effects of Xe and N2O. Significance Statement We could record pharmacologically isolated sEPSCNMDA and eEPSCNMDA and clearly detect all kinetic parameters of sEPSCNMDA and eEPSCNMDA at synaptic levels by using "synapse bouton preparation" of rat hippocampal CA3 neurons. We found that Xe and N2O clearly suppressed both sEPSCNMDA and eEPSCNMDA Different from previous studies, present results suggest that Xe and N2O predominantly inhibit the NMDA responses by presynaptic mechanisms.