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Isoflurane induced impairment of synaptic transmission in hippocampal neurons of the guinea pig in vitro

The effects of anaesthetic applications of isoflurane on 82 CA₁
neurons were studied in in vitro preparations (guinea pigs) using
intracellular recording techniques. Various parameters of their
excitability such as membrane electrical properties, action potentials and
their afterhyperpolarizing potentials as well as synaptic transmission were
determined during bath perfusion of clinically relevant concentrtaions of
isoflurane. Concentrations of isoflurane were detected in the bath with
¹⁹fluorine nuclear magnetic resonance techniques, and were found to range between 0.02 and 0.3 mM. No consistent effects on the membrane properties were observed. When synaptic activity was blocked by tetrodotoxin, isoflurane induced a hyperpolarization (3-5 mV) without affecting input conductance which was computed from the voltage responses to injections of hyperpolarizing current pulses and the slopes of current-voltage relations for each cell. Responses to depolarizing pulses revealed that the threshold, amplitude and duration of the evoked spikes were not greatly altered, although repetitive spike firing was suppressed in a dose-dependent manner by isoflurane. Similarly, the amplitude and duration of the long-lasting hyperpolarizations following the elicitation of multiple (4 or 5) spikes were reduced in a reversible and dose-dependent manner. Reductions in amplitude and duration of excitatory and inhibitory postsynaptic potentials evoked by electrical stimulation of stratum radiatum were observed; these effects also were strictly dependent on the dose, as well as on duration of the application. These investigations have revealed that isoflurane interferes with synaptic transmission in the hippocampal slice preparation and suggest that presynaptic actions on transmitter release, in addition to postsynaptic effects / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Identiferoai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/28027
Date January 1988
CreatorsMiu, Peter
PublisherUniversity of British Columbia
Source SetsUniversity of British Columbia
LanguageEnglish
Detected LanguageEnglish
TypeText, Thesis/Dissertation
RightsFor non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

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