Enhancement of Purkinje Neuronal Excitability by the Inhibition of Fast Voltage Gated K+ Channel Function in Ataxic Rats

Objective: The purpose of this study was to investigate the role of fast inactivating (IA) voltage dependent potassium channels in shaping the discharge activity of cerebellar Purkinje cells (PCs) in ataxic rats. Materials and Methods: Male Sprauge-Dawley rats (40-60 g) were used in this study. Ataxia was induced via single i.p. injection of 3-acethylpyridine (65 mg/kg). Four days following induction of ataxia, the rats were decapitated after being anesthetized using ether. 300 ?m thick parasagittal slices were prepared from the vermis of the cerebellum. Sharp intracellular recording was achieved from Purkinje cells under continuous superfusion of ACSF containing synaptic blockers. Results: Intracellular recording of 21 Purkinje neurons in cerebellar slice preparation showed that Purkinje cells of ataxic rats fire in three modes of tonic (23.81%), burst (19.05%) and silence (57.14%). Following the application of 4-AP, 83.33% of the silent PCs were spontaneously fired and the burst activity was robustly enhanced in bursting PCs. In addition, 4-AP significantly increased the duration of burst and active periods but decreased the duration of inactive period. It also increased the number of sodium spikes within each burst. Conclusion: 4-AP sensitive current in Purkinje cell of ataxic rat involves in three modes of firing pattern. In addition, the inhibition of fast inactivating potassium channels (IA) with 4-AP enhances the spontaneous discharge activity of Purkinje cells.