Effects of flecainide (a class IC antiarrhythmic drug) on the maximum rate of rise (Vmax) of action potentials (APs) were studied in guinea-pig papillary muscles, with special reference to their time, voltage, and action potential duration (APD) dependence in the presence and absence of nicorandil. Nicorandil was used to shorten APD, i.e., the time period of inactivation state of sodium channels. APs were recorded from the preparations using standard microelectrode techniques. Flecainide (5 mumol/l) reduced Vmax without changing resting potential, AP amplitude, APD50, and APD90 examined at 1 Hz. The drug shifted the normalized Vmax-membrane potential curve (examined at 1/60 Hz) in the hyperpolarizing direction by 3.1 +/- 0.8 mV (n = 6) (voltage dependence). The drug caused a frequency-dependent reduction of Vmax at greater than or equal to 0.1 Hz, developed a use-dependent reduction of Vmax at 1 Hz with an onset time constant of 11.7 +/- 0.4 s (n = 6), and slowed the recovery process of Vmax, whose resultant recovery time constant was 19.9 +/- 1.2 s (n = 6) (time dependence). These flecainide-induced time-dependent reductions of Vmax were not antagonized by nicorandil (1 mmol/l) which shortened APD to about 1/4 of control (APD independence). These results suggest that flecainide is primarily an open channel blocker because its channel-blocking actions are independent of APD or the time period of inactivation.