Anaesthetic depression of excitatory synaptic transmission in neocortex.
A decrease in synaptic excitation as well as an enhancement of neuronal inhibition in the central nervous system have been suggested as possible mechanisms of anaesthesia which we have investigated with intraneuronal recording techniques in neocortex. The effects of a volatile agent--isoflurane and a steroid preparation--Althesin, on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) evoked by epicortical electrical stimulation were investigated in in vitro slice preparations of anterior cingulate and sensorimotor cortices of guinea pig. Applications of isoflurane (0.5-2.5 minimum alveolar concentration or MAC) and Althesin (10-200 microM) induced a dose-dependent, reversible depression of EPSPs with EC50's of 1 MAC and approximately 50 microM respectively. In order to eliminate the possibilities of a shunting effect on EPSPs by the conductances involved in the concomitant IPSPs, a GABAA-antagonist (bicuculline) was applied together with the anaesthetics. With this IPSP blockade, both anaesthetics depressed the EPSPs and were effective in reducing the epileptiform activities evoked by bicuculline during the subpial stimulation. The IPSPs also were evoked during the blockade of K-conductances by internal Cs-applications in order that the effects of anaesthetics could be studied exclusively on the Cl-mediated GABAergic IPSPs. Both isoflurane (0.5-2.5 MAC) and Althesin (10-100 microM) depressed the IPSPs in a dose dependent manner. These investigations demonstrate that applications of isoflurane and Althesin depressed the excitabilities of neocortical neurons by interfering with synaptic excitation, possibly at pre- and postsynaptic sites, rather than by potentiating neuronal inhibition.
el-Beheiry
H
H
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
E
E
D000200:Action Potentials / Q000187:drug effects; D000530:Alfaxalone Alfadolone Mixture / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000777:Anesthetics; D002586:Cesium; D000530:Alfaxalone Alfadolone Mixture; D007530:Isoflurane; D001640:Bicuculline