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The Journal of Neuroscience, December 1, 1998, 18(23):9716-9726
Effect of Nitrous Oxide on Excitatory and Inhibitory Synaptic
Transmission in Hippocampal Cultures
Steven
Mennerick1,
Vesna
Jevtovic-Todorovic2,
Slobodan M.
Todorovic2,
Weixing
Shen1,
John W.
Olney1, and
Charles F.
Zorumski1
Departments of 1 Psychiatry and
2 Anesthesiology, Washington University School of Medicine,
St. Louis, Missouri 63110
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
GABAA receptor-mediated (GABAR) postsynaptic currents
likely caused by previously reported effects of N2O on
GABAA 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.
Key words:
NMDA receptor; glutamate; nitrous oxide; GABA; postsynaptic; presynaptic
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239716-11$05.00/0
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