title: Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons.
abstract: 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 GABA(A) 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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Kitamura
authors.forename: William
authors.initials: W
authors.lastname: Marszalec
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Yeh
authors.forename: Toshio
authors.initials: T
authors.lastname: Narahashi
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D015222:Sodium Channels; D013779:Tetrodotoxin; D006221:Halothane; D015742:Propofol