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Vol. 304, Issue 1, 162-171, January 2003
Department of Molecular Pharmacology and Biological Chemistry,
Northwestern University Medical School, Chicago, Illinois
General anesthetics are thought to act on both excitatory and
inhibitory neuronal pathways at both post- and presynaptic sites. However, the literature in these regards is somewhat controversial. The
aim of the present study was to reassess the relative importance of the
various anesthetic actions using a common preparation. Rat cortical
neurons in primary culture were used to record spontaneous miniature
postsynaptic currents by the whole-cell patch-clamp technique.
Halothane at clinically relevant concentrations prolonged the decay
phase of spontaneous miniature inhibitory postsynaptic currents
(mIPSCs) recorded in the presence of tetrodotoxin and at higher
concentrations decreased the frequency of mIPSCs. The mIPSC amplitudes
underwent little change. Spontaneous action potential-dependent IPSCs
recorded in the absence of tetrodotoxin were similarly affected by
halothane. Halothane also decreased the frequency of spontaneous miniature non-N-methyl-D-aspartate (NMDA)
excitatory postsynaptic currents (mEPSCs) as well as spontaneous action
potential-dependent NMDA EPSCs and non-NMDA EPSCs without affecting
their decay phase. The halothane effect on mIPSC and mEPSC frequency
was dependent on the external calcium concentration. In contrast to
halothane, the only effect of propofol was the prolongation of the
decay phase of mIPSCs and IPSCs. The prolongation of mIPSCs and IPSCs by halothane and propofol coupled with the ineffectiveness on mEPSCs
and EPSCs suggests a selective postsynaptic modulation of
GABAA receptors. The additional calcium-dependent
inhibition of mIPSC and mEPSC frequency by halothane (but not propofol)
suggests a more general mechanism by this anesthetic on presynaptic
transmitter release.
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