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

Verapamil is a widely used Ca(2+) 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 microM. However, verapamil reversibly inhibited I(Kur) in a concentration-dependent manner (IC(50) = 3.2 microM). At test potential of +50 mV, 5 microM 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.