Inhibition of ultra-rapid delayed rectifier K+ current by verapamil in human atrial myocytes

Verapamil is a widely used Ca2+ channel antagonist in the treatment of cardiovascular disorders including atrial arrhythmias. However, it is unknown whether the drug would inhibit the repolarization currents transient outward K+ current (I-to1) and ultra-rapid delayed rectifier K+ current (I-Kur) in human atrium. With whole-cell patch configuration, we evaluated effects of verapamil on I-to1 and I-Kur in isolated human atrial myocytes. It was found that verapamil did not decrease I-to1 at 1-50 muM. However, verapamil reversibly inhibited I-Kur in a concentration-dependent manner (IC50 = 3.2 W). At test potential of +50 mV, 5 muM verapamil decreased I-Kur by 61.3 +/- 7.5%. Verapamil significantly accelerated inactivation of I-Kur, suggesting an open channel block mechanism. The results indicate that verapamil significantly blocks the repolarization K+ current I-Kur, but not I-to1, in human atrial atrium, which may account at least in part for the atrial effect of the drug. (C) 2003 Elsevier Ltd. All rights reserved.