PROPAFENONE PREFERENTIALLY BLOCKS THE RAPIDLY ACTIVATING COMPONENT OFDELAYED RECTIFIER K-PIG VENTRICULAR MYOCYTES - VOLTAGE-INDEPENDENT AND TIME-DEPENDENT BLOCK OF THE SLOWLY ACTIVATING COMPONENT( CURRENT IN GUINEA)

The effects of propafenone on the delayed rectifier Kf current were st udied in guinea pig ventricular myocytes by using the patch-clamp tech nique. In these myocytes, this current consists of at least two compon ents: a La3+-sensitive component activating rapidly with moderate depo larizations and a La3+-resistant current slowly activating at more pos itive potentials. In the absence of La3+ (when both components are pre sent), propafenone inhibited the delayed outward current, its effects being more marked after weak than after strong depolarizations. Propaf enone-induced block of the tail currents elicited on return to -30 mV was more marked after short than after long depolarizing pulses. In th e presence of 1 mu mol/L propafenone, the envelope-of-tails test was s atisfied, thus indicating that at this concentration propafenone compl etely blocks the rapidly activating component. In the presence of La3 (when only the slow component is present), the steady state inhibitio n induced by 5 mu mol/L propafenone on both the maximum activated and the tail currents was independent of the test pulse voltage. Developme nt of propafenone-induced block on the slowly activating component was very fast and linked to channel opening. In addition, the blockade ap peared to be use dependent, with the rate constant of the onset kineti cs at 2 Hz being 0.44+/-0.1 pulse(-1). The recovery process from propa fenone-induced block exhibited a time constant of 2.5+/-0.4 s. These r esults indicated that propafenone preferentially inhibits the rapidly activating component of the delayed rectifier and that it blocks in a voltage-independent and time-dependent manner the slow component of th is current.