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

Abstract

It is unknown whether the widely used L-type Ca 2+ channel antagonists diltiazem and nifedipine would block the repolarization K + currents, transient outward current (I tol) 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 tol and I Kur in human atrial myocytes with whole-cell patch-clamp technique. It was found that diltiazem substantially inhibited I tol in a concentration-dependent manner, with an IC 50 of 29.2 ± 2.4 μM, and nifedipine showed a similar effect (IC 50 = 26.8 ± 2.1 μM). The two drugs had no effect on voltage-dependent kinetics of the current; however, they accelerated I tol inactivation significantly, suggesting an open channel block. In addition, diltiazem and nifedipine suppressed I Kur in a concentration-dependent manner (at + 50 mV, IC 50 = 11.2 ± 0.9 and 8.2 ± 0.8 μM, respectively). These results indicate that the Ca 2+ channel blockers diltiazem and nifedipine substantially inhibit I tol and I Kur in human atrial myocytes. © 2005 Nature Publishing Group All rights reserved.link_to_OA_fulltex