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Publication
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Antkowiak, B. and D. Heck: Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices. Journal of Neurophysiology 77, 2525-2538 (1997)
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Abstract:
The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on gamma-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,
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 mu M 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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