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 (Ito1) and ultra-rapid delayed rectifier K+ current (IKur) in human atrium. With whole-cell patch configuration, we evaluated effects of verapamil on Ito1 and IKur in isolated human atrial myocytes. It was found that verapamil did not decrease Ito1 at 1–50 μM. However, verapamil reversibly inhibited IKur in a concentration-dependent manner (IC50 = 3.2 μM). At test potential of +50 mV, 5 μM verapamil decreased IKur by 61.3 ± 7.5%. Verapamil significantly accelerated inactivation of IKur, suggesting an open channel block mechanism. The results indicate that verapamil significantly blocks the repolarization K+ current IKur, but not Ito1, in human atrial atrium, which may account at least in part for the atrial effect of the drug.