Effects of propafenone on K currents in human atrial myocytes

摘要

The class Ic anti-arrhythmic agent, flecainide is known to inhibit the transient outward K current (Ito) selectively in human atrium. We studied the effects of propafenone, another class Ic anti-arrhythmic agent, on K currents in human atrial myocytes using a whole-cell voltage-clamp method.Propafenone inhibited both Ito and the sustained or ultra-rapid delayed rectifier K current (Isus or Ikur) evoked by depolarization pulses. The concentration for half-maximal inhibition (IC50) was 4.9 μM for Ito and 8.6 μM for Isus. Propafenone blocked Ito and Isus in a voltage- and use-independent fashion and accelerated the inactivation time constant of Ito [from 28.3 to 6.7 ms at 10 μM propafenone].The steady-state inactivation curve for Ito was unaffected by propafenone. Propafenone did not affect the initial current at depolarizing potentials, but it did produce a block that increased as a function of time after depolarization (time constant of 3.4 ms). This suggests that propafenone preferentially blocked Ito in the open state.Propafenone had no significant effect on the rate at which Ito recovered from inactivation at −80 mV suggesting that propafenone dissociates rapidly from the channel.The steady-state activation curve for Isus was not affected by propafenone. Propafenone slowed the time course of the onset of the Isus tail current. This suggests that propafenone blocked Isus in the open state.The present results suggest that, unlike flecainide, propafenone blocks both Ito and Isus in human atrial myocytes in the open state at clinically relevant concentrations.