Effects of diltiazem and nifedipine on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes

1 It is unknown whether the widely used L-type Ca2+ channel antagonists diltiazem and nifedipine would block the repolarization K+ currents, transient outward current (I-to1) and ultra-rapid delayed rectifier K+ current (I-Kur), in human atrium. The present study was to determine the effects of diltiazem and nifedipine on I-to1 and IKur in human atrial myocytes with whole-cell patch-clamp technique. 2 It was found that diltiazem substantially inhibited I-to1 in a concentration-dependent manner, with an IC50 of 29.2+/-2.4 muM, and nifedipine showed a similar effect (IC50 = 26.8+/-2.1 muM). The two drugs had no effect on voltage-dependent kinetics of the current; however, they accelerated I-to1 inactivation significantly, suggesting an open channel block. 3 In addition, diltiazem and nifedipine suppressed I-Kur in a concentration-dependent manner (at +50 mV, IC50 = 11.2+/-0.9 and 8.2+/-0.8 muM, respectively). These results indicate that the Ca2+ channel blockers diltiazem and nifedipine substantially inhibit I-to1 and IKur in human atrial myocytes.