AuthorsM. Maleckar, J. L. Greenstein, W. R. Giles and N. A. Trayanova
TitleK+ Current Changes Account for the Rate Dependence of the Action Potential in the Human Atrial Myocyte
AfilliationCenter for Biomedical Computing (SFF), Cardiac Modeling, Scientific Computing
Project(s)Center for Biomedical Computing (SFF)
StatusPublished
Publication TypeJournal Article
Year of Publication2009
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Number4
Pagination1398-1410
Date PublishedOctober
Abstract

Ongoing investigation of the electrophysiology and pathophysiology of the human atria requires an accurate representation of the membrane dynamics of the human atrial myocyte. However, existing models of the human atrial myocyte action potential do not accurately reproduce experimental observations with respect to the kinetics of key repolarizing currents or rate dependence of the action potential and fail to properly enforce charge conservation, an essential characteristic in any model of the cardiac membrane. In addition, recent advances in experimental methods have resulted in new data regarding the kinetics of repolarizing currents in the human atria. The goal of this study was to develop a new model of the human atrial action potential, based on the Nygren et al. model of the human atrial myocyte and newly available experimental data, that ensures an accurate representation of repolarization processes and reproduction of action potential rate dependence and enforces charge conservation. Specifically, the transient outward K(+) current (I(t)) and ultrarapid rectifier K(+) current (I(Kur)) were newly formulated. The inwardly recitifying K(+) current (I(K1)) was also reanalyzed and implemented appropriately. Simulations of the human atrial myocyte action potential with this new model demonstrated that early repolarization is dependent on the relative conductances of I(t) and I(Kur), whereas densities of both I(Kur) and I(K1) underlie later repolarization. In addition, this model reproduces experimental measurements of rate dependence of I(t), I(Kur), and action potential duration. This new model constitutes an improved representation of excitability and repolarization reserve in the human atrial myocyte and, therefore, provides a useful computational tool for future studies involving the human atrium in both health and disease.

Notes

Should be listed in 2010 Annual Report

Citation KeySimula.SC.450