K+ current changes account for the rate dependence of the action potential in the human atrial myocyte
K+ current changes account for the rate dependence of the action potential in the human atrial myocyte
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DOI：
10.1152/ajpheart.00411.2009
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发表时间：
2009-10-01
影响因子：
4.8
通讯作者：
Trayanova, Natalia A.
中科院分区：
文献类型：
--
作者：
Maleckar, Mary M.;Greenstein, Joseph L.;Trayanova, Natalia A.
Maleckar MM，Greenstein JL，Giles WR，Trayanova NA.钾离子电流的变化占率依赖性的动作电位在人心房肌细胞。美国生理学杂志心脏循环生理学297：H1398-H1410，2009年。首次发表于2009年7月24日; doi：10.1152/ajpheart.00411.2009。人类心房的电生理学和病理生理学的持续研究需要人类心房肌细胞的膜动力学的准确表示。然而，现有的人类心房肌细胞动作电位模型不能准确地再现关于动作电位的关键复极化电流或速率依赖性的动力学的实验观察，并且不能正确地执行电荷守恒，这是任何心脏膜模型中的基本特征。此外，实验方法的最新进展导致了关于人类心房复极化电流动力学的新数据。本研究的目的是基于Nygren等人的人心房肌细胞模型和新获得的实验数据开发一种新的人心房动作电位模型，确保复极过程的准确表示和动作电位速率依赖性的再现，并强制电荷守恒。特别是，瞬时外向钾电流（I-t）和超快速整流钾电流（I-Kur）的新公式。对内向整流K+电流（I-K1）进行了重新分析，并进行了适当的实施。人心房肌细胞动作电位与这个新的模型的模拟表明，早期复极依赖于I-t和I-Kur的相对电导，而I-Kur和I-K1的密度的基础后来复极。此外，该模型再现了I-t，I-Kur和动作电位时程的速率依赖性的实验测量。这个新的模型构成了一个改进的代表性的兴奋性和复极储备在人类心房肌细胞，因此，提供了一个有用的计算工具，为未来的研究涉及人类心房在健康和疾病。
Maleckar MM, Greenstein JL, Giles WR, Trayanova NA. K+ current changes account for the rate dependence of the action potential in the human atrial myocyte. Am J Physiol Heart Circ Physiol 297: H1398-H1410, 2009. First published July 24, 2009; doi: 10.1152/ajpheart.00411.2009.-Ongoing investigation of the electrophysiology and pathophysiology of the human atria requires an accurate representation of the membrane dynamics of the human atrial myocyte. However, existing models of the human atrial myocyte action potential do not accurately reproduce experimental observations with respect to the kinetics of key repolarizing currents or rate dependence of the action potential and fail to properly enforce charge conservation, an essential characteristic in any model of the cardiac membrane. In addition, recent advances in experimental methods have resulted in new data regarding the kinetics of repolarizing currents in the human atria. The goal of this study was to develop a new model of the human atrial action potential, based on the Nygren et al. model of the human atrial myocyte and newly available experimental data, that ensures an accurate representation of repolarization processes and reproduction of action potential rate dependence and enforces charge conservation. Specifically, the transient outward K+ current (I-t) and ultrarapid rectifier K+ current (I-Kur) were newly formulated. The inwardly recitifying K+ current (I-K1) was also reanalyzed and implemented appropriately. Simulations of the human atrial myocyte action potential with this new model demonstrated that early repolarization is dependent on the relative conductances of I-t and I-Kur, whereas densities of both I-Kur and I-K1 underlie later repolarization. In addition, this model reproduces experimental measurements of rate dependence of I-t, I-Kur, and action potential duration. This new model constitutes an improved representation of excitability and repolarization reserve in the human atrial myocyte and, therefore, provides a useful computational tool for future studies involving the human atrium in both health and disease.