Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures

Steven Mennerick, Vesna Jevtovic-Todorovic, Slobodan M. Todorovic, Weixing Shen, John W. Olney, Charles F. Zorumski

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Nitrous oxide (N2O; laughing gas) has been a widely used anesthetic/analgesic since the 19th century, although its cellular mechanism of action is not understood. Here we characterize the effects of N2O on excitatory and inhibitory synaptic transmission in microcultures of rat hippocampal neurons, a preparation in which anesthetic effects on monosynaptic communication can be examined in a setting free of polysynaptic network variables. Eighty percent N2O occludes peak NMDA receptor-mediated (NMDAR) excitatory autaptic currents (EACs) with no effect on the NMDAR EAC decay time course. N2O also mildly depresses AMPA receptor-mediated (AMPAR) EACs. We find that N2O inhibits both NMDA and non-NMDA receptor-mediated responses to exogenous agonist. The postsynaptic blockade of NMDA receptors exhibits slight apparent voltage dependence, whereas the blockade of AMPA receptors is not voltage dependent. Although the degree of ketamine and Mg2+ blockade of NMDA-induced responses is dependent on permeant ion concentration, the degree of N2O blockade is not. We also observe a slight and variable prolongation of GABA(A) receptor-mediated (GABAR) postsynaptic currents likely caused by previously reported effects of N2O on GABA(A) receptors. Despite the effects of N2O on both NMDA and non-NMDA ionotropic receptors, glial glutamate transporter currents and metabotropic glutamate receptor-mediated synaptic depression are not affected. Paired-pulse depression, the frequency of spontaneous miniature excitatory synaptic currents, and high-voltage-activated calcium currents are not affected by N2O. Our results suggest that the effects of N2O on synaptic transmission are confined to postsynaptic targets.

Original languageEnglish
Pages (from-to)9716-9726
Number of pages11
JournalJournal of Neuroscience
Issue number23
StatePublished - Dec 1 1998


  • GABA
  • Glutamate
  • NMDA receptor
  • Nitrous oxide
  • Postsynaptic
  • Presynaptic


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