TY - JOUR
T1 - Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices
AU - Antkowiak, Bernd
AU - Heck, Detlef
PY - 1997
Y1 - 1997
N2 - 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.
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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U2 - 10.1152/jn.1997.77.5.2525
DO - 10.1152/jn.1997.77.5.2525
M3 - Article
C2 - 9163374
AN - SCOPUS:0030979403
SN - 0022-3077
VL - 77
SP - 2525
EP - 2538
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 5
ER -