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 effectsMedicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat