A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates

Aman Mahajan, Yohannes Shiferaw, Daisuke Sato, Ali Baher, Riccardo Olcese, Lai Hua Xie, Ming Jim Yang, Peng Sheng Chen, Juan G. Restrepo, Alain Karma, Alan Garfinkel, Zhilin Qu, James N. Weiss

Research output: Contribution to journalArticle

256 Scopus citations

Abstract

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 I Ca,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.

Original languageEnglish (US)
Pages (from-to)392-410
Number of pages19
JournalBiophysical journal
Volume94
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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    Mahajan, A., Shiferaw, Y., Sato, D., Baher, A., Olcese, R., Xie, L. H., Yang, M. J., Chen, P. S., Restrepo, J. G., Karma, A., Garfinkel, A., Qu, Z., & Weiss, J. N. (2008). A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates. Biophysical journal, 94(2), 392-410. https://doi.org/10.1529/biophysj.106.98160