Nygren A, Fiset C, Firek L, Clark J W, Lindblad D S, Clark R B, Giles W R
Department of Electrical and Computer Engineering, Rice University, Houston, Tex 77005-1892, USA.
Circ Res. 1998;82(1):63-81. doi: 10.1161/01.res.82.1.63.
We have developed a mathematical model of the human atria myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley-type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K+ current (I[sus]), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K+ current, I(sus) and L-type Ca2+ current (I[Ca,L]) and that the role of I(sus) in the human atrial action potential can be modulated by the baseline sizes of I(Ca,L), I(sus) and the rapid delayed rectifier K+ current. As a result, our simulations suggest that the functional role of I(sus) can depend on the physiological/disease state of the cell.
我们基于从分离的单个心肌细胞记录的平均电压钳数据，开发了一种人类心房肌细胞的数学模型。我们的模型由一个用于肌膜的霍奇金 - 赫胥黎型等效电路，与一个流体隔室模型耦合而成，该流体隔室模型考虑了细胞质以及肌浆网中离子浓度的变化。这种公式化表述能够重建代表我们实验室中大多数人类心房细胞记录的动作电位数据，因此提供了基于生物物理学的潜在离子电流解释。这项工作部分基于我们团队之前发表的兔心房肌细胞模型，其动机源于人类和兔心房之间一些复极电流的差异。因此，我们特别关注持续外向钾电流（I[sus]），它可能在决定人类心房动作电位的持续时间方面起重要作用。我们的结果表明，动作电位峰值和平台期的形状主要由瞬时外向钾电流、I(sus)和L型钙电流（I[Ca,L]）决定，并且I(sus)在人类心房动作电位中的作用可由I(Ca,L)、I(sus)和快速延迟整流钾电流的基线大小调节。因此，我们的模拟表明I(sus)的功能作用可能取决于细胞的生理/疾病状态。
