Journal
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Volume 384, Issue 1, Pages 187-196Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.122.001346
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In this study, we investigated how Xe and N2O modulate NMDA receptor-mediated spontaneous and evoked excitatory post-synaptic currents (sEPSC(NMDA) and eEPSC(NMDA)) in a synapse bouton preparation of rat hippocampal CA3 neurons. We found that Xe and N2O significantly decreased the frequency and amplitude of sEPSC(NMDA) without altering its decay time constant, and also decreased the amplitude but increased the Rf and PPR of eEPSC(NMDA) without altering its decay time constant. These results suggest that the inhibitory effects of Xe and N2O on synapse activity are primarily due to presynaptic mechanisms.
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 (sEPSC(NMDA) and eEPSC(NMDA)). This preparation is a mechanically isolated single neuron attached with nerve endings (boutons) preserving normal physiologic function and promoting the exact evaluation of sEPSC(NMDA) and eEPSC(NMDA) responses without influence of extrasynaptic, glial, and other neuronal tonic currents. These sEPSCs and eEPSCs are elicited by spontaneous glutamate release from many homologous glutamatergic boutons and by focal paired-pulse electric stimulation of a single bouton, respectively. The s/eEPSC(AMPA/KA) and s/eEPSC(NMDA) were isolated pharmacologically by their specific antagonists. Thus, independent contributions of pre- and postsynaptic responses could also be quantified. All kinetic properties of s/eEPSC(AMPA/KA) and s/eEPSC(NMDA) were detected clearly. The s/eEPSC(NMDA) showed smaller amplitude and slower rise and 1/e decay time constant (tau(Decay)) than s/eEPSC(AMPA/KA). Xe (70%) and N2O (70%) significantly decreased the frequency and amplitude without altering the tau(Decay) of sEPSC(NMDA). They also decreased the amplitude but increased the Rf and PPR without altering the tau(Decay) of the eEPSC(NMDA). These data show clearly that synapse bouton preparation can be an accurate model for evaluating s/eEPSC(NMDA). 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.
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