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PMID: 15345532 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A computational model of the human left-ventricular epicardial myocyte.

Biophysical journal ·Vol. 87 ·No. 3 ·2004-09-00 ·Pages 1507-25

Iyer V, Mazhari R, Winslow RL

Abstract

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, Ca(2+)-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.

MeSH Terms
Algorithms Arrhythmias, Cardiac/pathology Biophysical Phenomena Biophysics Calcium/chemistry,metabolism Calcium Channels/chemistry Calcium-Transporting ATPases/metabolism Heart Ventricles/anatomy & histology Humans Ions Kinetics Markov Chains Models, Statistical Models, Theoretical Potassium/chemistry Sarcoplasmic Reticulum Calcium-Transporting ATPases Sodium/chemistry Software Time Factors Ventricular Function
Chemicals
Calcium Channels Ions Sodium Sarcoplasmic Reticulum Calcium-Transporting ATPases Calcium-Transporting ATPases Potassium Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Iyer Vivek
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 21093, USA.
Mazhari Reza
Winslow Raimond L
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1529/biophysj.104.043299
Published
2004-09-00
Pages
1507-25
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1304558
Subset
IM
Grants
NHLBI NIH HHS · R01 HL061711 · United States
NHLBI NIH HHS · R01 HL105239 · United States
NHLBI NIH HHS · R01 HL-60133 · United States
NHLBI NIH HHS · R01 HL072488 · United States
NHLBI NIH HHS · R01 HL-61711 · United States
NHLBI NIH HHS · R01 HL-72488 · United States
NHLBI NIH HHS · R01 HL060133 · United States
NHLBI NIH HHS · P50 HL-52307 · United States
NHLBI NIH HHS · N01 HV28180 · United States
NHLBI NIH HHS · N01HV28180 · United States
External Links
PubMed source DOI: 10.1529/biophysj.104.043299 PMC Full Text View journal details
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