Rate-Dependent Role of IKur in Human Atrial Repolarization and Atrial Fibrillation Maintenance

Biophysical Journal
Martin AguilarS Nattel

Abstract

The atrial-specific ultrarapid delayed rectifier K+ current (IKur) inactivates slowly but completely at depolarized voltages. The consequences for IKur rate-dependence have not been analyzed in detail and currently available mathematical action-potential (AP) models do not take into account experimentally observed IKur inactivation dynamics. Here, we developed an updated formulation of IKur inactivation that accurately reproduces time-, voltage-, and frequency-dependent inactivation. We then modified the human atrial cardiomyocyte Courtemanche AP model to incorporate realistic IKur inactivation properties. Despite markedly different inactivation dynamics, there was no difference in AP parameters across a wide range of stimulation frequencies between the original and updated models. Using the updated model, we showed that, under physiological stimulation conditions, IKur does not inactivate significantly even at high atrial rates because the transmembrane potential spends little time at voltages associated with inactivation. Thus, channel dynamics are determined principally by activation kinetics. IKur magnitude decreases at higher rates because of AP changes that reduce IKur activation. Nevertheless, the relative contribution o...Continue Reading

Citations

Dec 24, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Haibo NiWayne R Giles
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Sarah HilderinkArie O Verkerk
Feb 14, 2019·International Journal of Cardiology·Konstantinos N AronisNatalia A Trayanova
Oct 8, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Cesare CorradoSteven A Niederer

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