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Effects of the volatile anesthetic enflurane on
spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje
cells in rat cerebellar slices.
Antkowiak B, Heck D.
Max-Planck-Institut fur Biologische Kybernetik, Tuebingen, Germany.
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(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 microM
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.
PMID: 9163374 [PubMed - indexed for MEDLINE]
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