Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization

Although inactivation of the rapidly activating delayed rectifier current (I-Kr) limits outward current on depolarization, the role of I-Kr (and recovery from inactivation) during repolarization is uncertain. To characterize I-Kr during ventricular repolarization (and compare with the inward rectifier current, I-K1), voltage-clamp waveforms simulating the action potential were applied to canine ventricular, atrial, and Purkinje myocytes. In ventricular myocytes, I-Kr was minimal at plateau potentials but transiently increased during repolarizing ramps. The I-Kr transient was unaffected by repolarization rate and maximal after 150-ms depolarizations (+25 mV). Action potential clamps revealed the I-Kr transient terminating the plateau. Although peak I-Kr transient density was relatively uniform among myocytes, potentials characterizing the peak transients were widely dispersed. In contrast, peak inward rectifier current (I-K1) density during repolarization was dispersed, whereas potentials characterizing I-K1 defined a narrower (more negative) voltage range. In summary rapidly activating I-Kr provides a delayed voltage-dependent (and functionally time-independent) outward transient during ventricular repolarization, consistent with rapid recovery from inactivation. The heterogeneous voltage dependence of I-Kr provides a novel means for modulating the contribution of this current during repolarization.