Pilsicainide, a class Ic agent, is known to be an effective drug parti
cularly for treating atrial tachyarrhythmias. However, its electrophys
iological effects on the atrium have not been well studied. To charact
erize the electrophysiologic effects of pilsicainide on atrial myocyte
s in class Ic drugs, we examined the effects of this drug on membrane
currents in single rabbit atrial myocytes using the tight-seal whole c
ell voltage-clamp technique. Under the current-clamp condition, pilsic
ainide did not affect the action potential duration at therapeutic ran
ges (less than or equal to 3 mu M) and slightly shortened it at higher
concentrations (greater than or equal to 10 mu M). These observations
were quite different from those with other class Ic agents including
flecainide and propafenone which prolong the atrial action potential d
uration. The drug did not affect the resting membrane potential. Under
the voltage-clamp condition, pilsicainide inhibited the transient out
ward current (I-to) that is more prominent in the atrium than in the v
entricle in a concentration-dependent manner. However, in contrast to
other class Ic agents, the inhibition of I-to by pilsicainide was obse
rved only at much higher concentrations (IC(50)similar to 300 mu M) an
d did not affect the inactivation time-course of I,. Moreover, the dru
g (10 mu M) did not significantly affect the Ca2+, delayed rectifier K
+, inward rectifying K+, acetylcholine-induced K+ or ATP-sensitive Kcurrents. From these results, pilsicainide could be differentiated as
a pure Na+ channel blocker from other class Ic agents with diverse eff
ects on membrane currents and should be recognized accordingly in clin
ical situations.