Effects of the volatile anaesthetic enflurane on spontaneous discharge rate
and GABAA-mediated inhibition of Purkinje cells in rat cerebellar slices.
Bernd Antkowiak, Detlef Heck.
Max-Planck-Institut fr Biologische Kybernetik, Spemannstr. 38, 72076
Tbingen, Germany.
APStracts 4:0042N, 1997.
ABSTRACT
The effects of the volatile anaesthetic enflurane on the spontaneous action
potential firing and on GABAA-mediated synaptic inhibition of Purkinje cells
were investigated in sagittal cerebellar slices. The anaesthetic shifted the
discharge patterns from continuous spiking towards 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 anaesthesia in 50%
of the patients and rats). When the GABAA-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. 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 (M tetrodotoxin. 1-2 MAC enflurane increased
GABAA-mediated inhibition of Purkinje cells by 97(20 - 159(38%. During
current-clamp recordings, the anaesthetic (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 anaesthetic, probably an accelerated
activation of an inwardly directed cationic current (Ih) and a depression of
spike afterhyperpolarizations.
Received 19 September 1996; accepted in final form 13 January 1997.
APS Manuscript Number J623-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 February 1997