Inhibition of potassium currents by the antiarrhythmic drug E4031 in rat taste receptor cells

Abstract

The effect of the class III antiarrhythmic agent E4031 was investigated on a non-cardiac preparation as a potential tool for studying potassium currents. Patch clamp recordings in the whole cell configuration were performed on dissociated rat taste cells. These cells possess a variety of potassium currents; they also conduct action potentials. Unlike its more specific action on a type of delayed rectifier channel in cardiac cells, three types of potassium currents were reversibly diminished in taste cells in the presence of E4031. These included transient, sustained, and inwardly-rectifying potassium currents. Activation properties were not altered but the inactivation curve was shifted to the left by approximately 10 mV. Inhibitions of whole cell currents were voltage-dependent, larger at depolarized potentials, but were never complete. E4031 significantly broadened the gustatory action potential and, at higher concentrations, inhibited spike height, suggesting an additional inhibitory effect on sodium channels that was evident in voltage-clamp records. We conclude that E4031 is an effective inhibitor of potassium currents in the micromolar range and that it likely acts at a conserved segment of the potassium channel.