Open AccessDepression of Synaptic N-methyl-D-Aspartate Responses by Xenon and Nitrous Oxide
Author(s) -
Naoki Kotani,
IlSung Jang,
Michiko Nakamura,
Kiku aka,
Hideaki Nagami,
Norio Akaike
Publication year - 2022
Publication title -
the journal of pharmacology and experimental therapeutics/the journal of pharmacology and experimental therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.286
H-Index - 225
eISSN - 1521-0103
pISSN - 0022-3565
DOI - 10.1124/jpet.122.001346
Subject(s) - excitatory postsynaptic potential , inhibitory postsynaptic potential , nmda receptor , neuroscience , postsynaptic current , postsynaptic potential , chemistry , glutamate receptor , glutamatergic , biophysics , neurotransmission , post tetanic potentiation , receptor , biology , biochemistry
In "synapse bouton preparation" of rat hippocampal CA3 neurons, we examined how Xe and N 2 O 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 ( τ Decay ) than s/eEPSC AMPA/KA Xe (70%) and N 2 O (70%) significantly decreased the frequency and amplitude without altering the τ Decay of sEPSC NMDA They also decreased the amplitude but increased the Rf and PPR without altering the τ 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 N 2 O. SIGNIFICANCE STATEMENT: We could record pharmacologically isolated NMDA receptor-mediated spontaneous and (action potential-evoked) excitatory postsynaptic currents (sEPSC NMDA and eEPSC NMDA ) and clearly detect all kinetic parameters of sEPSC NMDA and eEPSC NMDA at synaptic levels by using "synapse bouton preparation" of rat hippocampal CA3 neurons. We found that Xe and N 2 O clearly suppressed both sEPSC NMDA and eEPSC NMDA . Different from previous studies, present results suggest that Xe and N 2 O predominantly inhibit the NMDA responses by presynaptic mechanisms.