Iyer Vivek, Mazhari Reza, Winslow Raimond L
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.
Biophys J. 2004 Sep;87(3):1507-25. doi: 10.1529/biophysj.104.043299.
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.
本文提出了一种人类左心室心外膜心肌细胞的计算模型。利用从重组人类离子通道研究和/或从人类左心室心外膜分离的单个心肌细胞的全细胞记录中获得的实验数据，对这些细胞中存在的每种主要离子电流模型进行了构建和验证。对快速钠电流、瞬时外向电流、延迟整流电流的快速成分和L型钙电流的门控连续时间马尔可夫链模型进行了修改，以在生理温度下表示人类数据。针对延迟整流电流的慢成分门控构建了一个新模型，并根据实验数据进行了验证。改变了钙处理和交换电流的特性，以适当表示细胞内离子浓度的动态变化。该模型能够再现和预测实验中观察到的广泛行为，包括动作电位形态、离子电流、细胞内钙瞬变、动作电位持续时间的频率依赖性、Ca(2+) -频率关系以及期外收缩恢复/期外收缩后增强。因此，该模型是研究人类左心室心肌细胞心律失常机制和药物-通道相互作用后果的有用工具。
