Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. A patch-clamp study in adult mouse hippocampal slices.
BACKGROUND
The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date.


METHODS
The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists.


RESULTS
Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane.


CONCLUSIONS
Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.
Perouansky
M
M
Department of Anesthesiology and Critical Care, Hadassah University Hospital-Hebrew University, Jerusalem, Israel.
Baranov
D
D
Salman
M
M
Yaari
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D018408:Patch-Clamp Techniques; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D017470:Receptors, Glutamate; D006221:Halothane