The Journal of Neurophysiology Vol. 77 No. 5 May 1997, pp. 2525-2538
Copyright ©1997 The American Physiological Society

Effects of the Volatile Anesthetic Enflurane on Spontaneous Discharge Rate and GABA_A-Mediated Inhibition of Purkinje Cells in Rat Cerebellar Slices

Bernd Antkowiak and Detlef Heck

Max-Planck-Institut für Biologische Kybernetik, 72076 Tuebingen, Germany

Antkowiak, Bernd and Detlef Heck. Effects of the volatileanesthetic enflurane on spontaneous discharge rate and GABA_A-mediated inhibition of Purkinje cells in rat cerebellar slices.J. Neurophysiol. 77: 2525-2538, 1997. The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on -aminobutyric acid-A (GABA_A)-mediated synaptic inhibition of Purkinje cells were investigated in sagittal cerebellar slices. The anesthetic shifted the discharge patterns from continuous spiking toward burst firing and decreased the frequency of extracellularly recorded spontaneous action potentials in a concentration-dependent manner. Half-maximal reduction was observed at a concentration corresponding to 2 MAC (1 MAC induces general anesthesia in 50% of patients and rats). When the GABA_A antagonist bicuculline was present, 2 MAC enflurane reduced action potential firing only by 13 ± 8% (mean ± SE). In further experiments, inhibitory postsynaptic currents (IPSCs) were monitored in the whole cell patch-clamp configuration from cells voltage clamped close to 80 mV. At 1 MAC, enflurane attenuated the mean amplitude of IPSCs by 54 ± 3% while simultaneously prolonging the time courses of monoexponential current decays by 413 ± 69%. These effects were similar when presynaptic action potentials were suppressed by 1 µM tetrodotoxin. At 1-2 MAC, enflurane increased GABA_A-mediated inhibition of Purkinje cells by 97 ± 20% to 159 ± 38%. During current-clamp recordings, the anesthetic (2 MAC) hyperpolarized the membrane potential by 5.2 ± 1.1 mV in the absence, but only by 1.6 ± 1.2 mV in the presence, of bicuculline. These results suggest that enflurane-induced membrane hyperpolarizations, as well as the reduction of spike rates, were partly caused by an increase in synaptic inhibition. Induction of burst firing was related to other actions of the anesthetic, probably an accelerated activation of an inwardly directed cationic current and a depression of spike afterhyperpolarizations.

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