EFFECTS OF THE VOLATILE ANESTHETIC ENFLURANE ON SPONTANEOUS DISCHARGERATE AND GABA(A)-MEDIATED INHIBITION OF PURKINJE-CELLS IN RAT CEREBELLAR SLICES

The effects of the volatile anesthetic enflurane on the spontaneous ac tion potential firing and on gamma-aminobutyric acid-A (GABA(A))-media ted synaptic inhibition of Purkinje cells were investigated in sagitta l cerebellar slices. The anesthetic shifted the discharge patterns fro m continuous spiking toward burst firing and decreased the frequency o f extracellularly recorded spontaneous action potentials in a concentr ation-dependent manner. Half-maximal reduction was observed at a conce ntration corresponding to 2 MAC (1 MAC induces general anesthesia in 5 0% of patients and rats). When the GABA, antagonist bicuculline was pr esent, 2 MAC enflurane reduced action potential firing only by 13 +/- 8% (mean +/- SE). In further experiments, inhibitory postsynaptic curr ents (IPSCs) were monitored in the whole cell patch-clamp configuratio n from cells voltage clamped close to -80 mV. At 1 MAC, enflurane atte nuated the mean amplitude of IPSCs by 54 +/- 3% while simultaneously p rolonging the time courses of monoexponential current decays by 413 +/ - 69%. These effects were similar when presynaptic action potentials w ere 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) hyperpol arized the membrane potential by 5.2 +/- 1.1 mV in the absence, but on ly by 1.6 +/- 1.2 mV in the presence, of bicuculline. These results su ggest that enflurane-induced membrane hyperpolarizations, as well as t he reduction of spike rates, were partly caused by an increase in syna ptic inhibition. Induction of burst firing was related to other action s of the anesthetic, probably an accelerated activation of an inwardly directed cationic current and a depression of spike afterhyperpolariz ations.