A computational model of the human left-ventricular epicardial myocyte
A computational model of the human left-ventricular epicardial myocyte
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DOI：
10.1529/biophysj.104.043299
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发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Winslow, RL
中科院分区：
文献类型：
--
作者：
Iyer, V;Mazhari, R;Winslow, RL
提出了人类左心室心外膜肌细胞的计算模型。使用重组人离子通道研究和/或从人左心室心外膜下分离的单个肌细胞的全细胞记录获得的实验数据来制定和验证这些细胞中存在的每种主要离子电流的模型。用于门控快速 Na+ 电流、瞬态外向电流、延迟整流器电流的快速分量和 L 型钙电流的连续时间马尔可夫链模型经过修改，以代表生理温度下的人体数据。制定了延迟整流器电流慢速分量门控的新模型，并根据实验数据进行了验证。钙处理和交换电流的特性被改变以适当地代表细胞内离子浓度的动态。该模型能够重现和预测实验观察到的各种行为，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、Ca2+-频率关系以及期外收缩恢复/期外收缩后增强。因此，该模型可作为研究心律失常机制和人类左心室肌细胞药物通道相互作用后果的有用工具。
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.