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.
Gintant
G A
GA
Cardiology Division, Department of Internal Medicine, and Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. gary.gintant@abbott.com
D000200:Action Potentials; D000818:Animals; D016275:Atrial Function; D004285:Dogs; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000166:cytology; D006352:Heart Ventricles / Q000166:cytology; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000166:cytology / Q000502:physiology; D016276:Ventricular Function