Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices

Bernd Antkowiak, Detlef Heck

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Abstract

The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on γ-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 I 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 after hyperpolarizations.

Original languageEnglish (US)
Pages (from-to)2525-2538
Number of pages14
JournalJournal of Neurophysiology
Volume77
Issue number5
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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Enflurane
Purkinje Cells
gamma-Aminobutyric Acid
Anesthetics
Action Potentials
Inhibitory Postsynaptic Potentials
Bicuculline
Aminobutyrates
GABA-A Receptor Antagonists
Tetrodotoxin
Membrane Potentials
General Anesthesia
Membranes
U 78517F

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

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title = "Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices",
abstract = "The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on γ-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 I 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 after hyperpolarizations.",
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AB - The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on γ-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 I 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 after hyperpolarizations.

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