Frequency- and voltage-dependent inhibition of delayed outward potassium current by flecainide in isolated atrial cell of guinea pig heart

Abstract

Effects of flecainide (Fle) on membrane currents were studied using an isolated single atrial cell from guinea pig hearts. The tight-seal cell clamp technique was used. In the current clamp condition, Fle prolonged significantly the atrial action potential (APD) with frequency dependence. Delayed outward K+ current and outward tail current were specifically inhibited by Fle in a frequency- and concentration-dependent fashion. Fle inhibited Ik more strongly as the membrane potential became more positive from +10 mV to +60 mV. The value of Ik was attenuated to 973 pA from 1105 pA of control and the value of tail current was reduced to 113 pA from 288 pA of control at 60 mV. The drug did not affect the holding current. The effects of Fle on the action potential and transmembrane ionic currents strongly suggested that the main mechanism of action of this agent was to inhibit the voltage-dependent potassium current. In the voltage clamp condition, Fle affected neither the conventional L type Ca2+ current nor the Ik1 current significantly. Our research proved that Fle was not completely consistent with the class Ic agents, because Fle could markedly increase the APD in the experiment.