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Biophysical Journal 94:392-410 (2008)
© 2008 The Biophysical Society

A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

Aman Mahajan * {dagger}, Yohannes Shiferaw {ddagger}, Daisuke Sato *, Ali Baher *, Riccardo Olcese * {dagger}, Lai-Hua Xie *, Ming-Jim Yang *, Peng-Sheng Chen §, Juan G. Restrepo ¶, Alain Karma ¶, Alan Garfinkel *, Zhilin Qu * and James N. Weiss *

* UCLA Cardiovascular Research Laboratory and the {dagger} Division of Molecular Medicine, Departments of Anesthesiology, Medicine (Cardiology), Physiology and Physiological Science, David Geffen School of Medicine at UCLA, Los Angeles, California; {ddagger} Department of Physics, California State University at Northridge, Northridge, California; § Division of Cardiology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California; and Department of Physics and Center for Interdisciplinary Research on Complex Systems, Northeastern University, Boston, Massachusetts

Correspondence: Address reprint requests to James N. Weiss, MD, Tel.: 310-825-9029; E-mail: jweiss{at}mednet.ucla.edu.

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35–37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.




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L.-H. Xie, D. Sato, A. Garfinkel, Z. Qu, and J. N. Weiss
Intracellular Ca Alternans: Coordinated Regulation by Sarcoplasmic Reticulum Release, Uptake, and Leak
Biophys. J., September 15, 2008; 95(6): 3100 - 3110.
[Abstract] [Full Text] [PDF]


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