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The Center for Cardiovascular Bioinformatics and Modeling and the Whitaker Biomedical Engineering Institute, The Johns Hopkins University School of Medicine and Whiting School of Engineering, Baltimore, Maryland
Correspondence: Address reprint requests to Raimond L. Winslow, PhD, Rm. 201B, Clark Hall, The Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21093. Tel.: 410-516-5417; Fax: 410-516-5294; E-mail: rwinslow{at}bme.jhu.edu.
A computational model of the human left-ventricular epicardial myocyte is presented. Models of each of the major ionic currents present in these cells are formulated and validated using experimental data obtained from studies of recombinant human ion channels and/or whole-cell recording from single myocytes isolated from human left-ventricular subepicardium. Continuous-time Markov chain models for the gating of the fast Na+ current, transient outward current, rapid component of the delayed rectifier current, and the L-type calcium current are modified to represent human data at physiological temperature. A new model for the gating of the slow component of the delayed rectifier current is formulated and validated against experimental data. Properties of calcium handling and exchanger currents are altered to appropriately represent the dynamics of intracellular ion concentrations. The model is able to both reproduce and predict a wide range of behaviors observed experimentally including action potential morphology, ionic currents, intracellular calcium transients, frequency dependence of action-potential duration, Ca2+-frequency relations, and extrasystolic restitution/post-extrasystolic potentiation. The model therefore serves as a useful tool for investigating mechanisms of arrhythmia and consequences of drug-channel interactions in the human left-ventricular myocyte.
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