A novel computational model of the human ventricular action potential and Ca transient.
A novel computational model of the human ventricular action potential and Ca transient.
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DOI：
10.1016/j.yjmcc.2009.09.019
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发表时间：
2010-01
影响因子：
5
通讯作者：
Bers DM
中科院分区：
文献类型：
--
作者：
Grandi E;Pasqualini FS;Bers DM
我们已经开发了一个详细的数学模型钙处理和离子电流在人心室肌细胞。我们的目标是：1）模拟基本的激发-收缩耦合现象; 2）使用真实的复极化K电流密度; 3）达到稳态。该模型依赖于我们小组先前开发的兔肌细胞模型的框架，具有肌膜下和连接区室，其中离子通道感测更高的[Ca] vs.散装胞质溶胶。离子通道和转运蛋白已被建模的基础上，最新的实验数据，从人心室肌细胞。已经制定了快速和缓慢灭活伊藤组分，以区分内皮细胞和心外膜肌细胞。还模拟了Ca处理蛋白和Na泵的梯度。该模型已被验证对一组广泛的实验数据，包括动作电位时程（APD）的适应和恢复，频率依赖性增加的Ca瞬态峰和[Na]i。有趣的是，快速心率下的Na蓄积是APD缩短的主要决定因素，通过Na泵和Na-Ca交换电流的向外移位。我们研究了阻断K电流对APD和复极储备的影响：IKs阻断不影响前者，并轻微降低后者; IK 1阻断适度增加APD，并更强烈地降低复极储备; IKr阻断剂显着延长APD，随着起搏频率的降低，这种影响加剧，与人心肌细胞的实验结果一致。我们的结论是，该模型提供了一个有用的框架，探讨兴奋收缩耦合机制和复极异常在单个心肌细胞水平。
We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: 1) simulate basic excitation-contraction coupling phenomena; 2) use realistic repolarizing K current densities; 3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of Ito have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na]i. Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: IKs block does not affect the former and slightly reduces the latter; IK1 blockade modestly increases APD and more strongly reduces repolarization reserve; IKr blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level.
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影响因子：
37.8
作者：
Jost, N;Virág, L;Varró, A
通讯作者：
Varró, A
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10.8
作者：
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作者：
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通讯作者：
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影响因子：
37.8
作者：
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通讯作者：
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