Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices.
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.
Antkowiak
B
B
Max-Planck-Institut für Biologische Kybernetik, Tuebingen, Germany.
Heck
D
D
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D046508:Culture Techniques; D004737:Enflurane / Q000494:pharmacology*; D005260:Female; D008297:Male; D008564:Membrane Potentials; D009433:Neural Inhibition / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D011963:Receptors, GABA-A; D004737:Enflurane