EFFECT OF NITROUS-OXIDE ON EXCITATORY AND INHIBITORY SYNAPTIC TRANSMISSION IN HIPPOCAMPAL CULTURES

Nitrous oxide (N2O; laughing gas) has been a widely used anesthetic/an algesic since the 19th century, although its cellular mechanism of act ion is not understood. Here we characterize the effects of N2O on exci tatory and inhibitory synaptic transmission in microcultures of rat hi ppocampal neurons, a preparation in which anesthetic effects on monosy naptic communication can be examined in a setting free of polysynaptic network variables. Eighty percent N2O occludes peak NMDA receptor-med iated (NMDAR) excitatory autaptic currents (EACs) with no effect on th e NMDAR EAC decay time course. N2O also mildly depresses AMPA receptor -mediated (AMPAR) EACs. We find that N2O inhibits both NMDA and non-NM DA 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. Alt hough the degree of ketamine and Mg2+ blockade of NMDA-induced respons es is dependent on permeant ion concentration, the degree of N2O block ade is not. We also observe a slight and variable prolongation of GABA (A) receptor-mediated (GABAR) postsynaptic currents likely caused by p reviously reported effects of N2O on GABA(A) receptors. Despite the ef fects of N2O on both NMDA and non-NMDA ionotropic receptors, glial glu tamate transporter currents and metabotropic glutamate receptor-mediat ed synaptic depression are not affected. Paired-pulse depression, the frequency of spontaneous miniature excitatory synaptic currents, and h igh-voltage-activated calcium currents are not affected by N2O. Our re sults suggest that the effects of N2O on synaptic transmission are con fined to postsynaptic targets.