Postsynaptic depression induced by isoflurane and Althesin in neocortical neurons.
The effects of two general anaesthetics, isoflurane--a volatile agent, and Althesin--a steroid preparation, were studied on the membrane electrical properties and spike activities of 64 neurons in in vitro slice preparations of neocortex excised from anterior cingulate and sensorimotor areas of guinea-pig brain. Spontaneous activity was depressed, and the thresholds for spikes evoked by intracellular injections of current pulses were increased in most neurons during applications of isoflurane in clinical concentrations (0.5-2.5 minimum alveolar concentration or MAC) and Althesin (15-100 microM). The MAC values are equivalent to 1-4% isoflurane in the gaseous phase. Applications in the higher ranges (1.5-2.5 MAC and 300-1500 microM) usually induced a small hyperpolarization (range, 3-8 mV) and an increase (10-30%) in input conductance. The repetitive spike firing evoked by current-pulse injections was inhibited and not uncommonly, abolished completely by an anaesthetic application. A striking feature in the actions of both agents on all neurons was the dose-dependent, reversible depression in amplitude and duration of the postspike afterhyperpolarizations (AHPs). These effects could not be attributed to anaesthetic induced changes in resting potentials, input conductances, or to the reduced number of evoked spikes. Bicuculline (50 microM) was applied concomitantly in 8 neurons with the anaesthetics to block Cl-conductances mediated by GABA-receptors that otherwise may "contaminate" the AHPs. In the presence of bicuculline, both anaesthetics produced a greater reduction in the amplitude and duration of the AHPs which are generated through Ca2+-mediated K+-conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
el-Beheiry
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
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D000530:Alfaxalone Alfadolone Mixture / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D000777:Anesthetics; D011963:Receptors, GABA-A; D000530:Alfaxalone Alfadolone Mixture; D007530:Isoflurane; D001640:Bicuculline