Wilders R, Kumar R, Joyner R W, Jongsma H J, Verheijck E E, Golod D, van Ginneken A C, Goolsby W N
Department of Medical Physiology and Sports Medicine, Utrecht University, The Netherlands.
Biophys J. 1996 Jan;70(1):281-95. doi: 10.1016/S0006-3495(96)79569-3.
We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded real cell action potentials was quite good, and the strength-duration curves for the real cells and for the LR model cell were in general correspondence. The experimental protocol allowed us to modify the effective size of either the simulation model or the real cell. 1) When we normalized real cell size to LR model cell size, required conductance for propagation between model cell and real cell was greater than that found for conduction between two LR model cells (5.4 nS), with a greater disparity when we stimulated the LR model cell (8.3 +/- 0.6 nS) than when we stimulated the real cell (7.0 +/- 0.2 nS). 2) Electrical loading of the action potential waveform was greater for real cell than for LR model cell even when real cell size was normalized to be equal to that of LR model cell. 3) When the size of the follower cell was doubled, required conductance for propagation was dramatically increased; but this increase was greatest for conduction from real cell to LR model cell, less for conduction from LR model cell to real cell, and least for conduction from LR model cell to LR model cell. The introduction of this "model clamp" technique allows testing of proposed membrane models of cardiac cells in terms of their source-sink behavior under conditions of extreme coupling by examining the symmetry of conduction of a cell pair composed of a model cell and a real cardiac cell. We have focused our experimental work with this technique on situations of extreme uncoupling that can lead to conduction block. In addition, the analysis of the geometrical factors that determine success or failure of conduction is important in the understanding of the process of discontinuous conduction, which occurs in myocardial infarction.
我们使用豚鼠心室细胞的罗和鲁迪(LR)数学模型,并结合实验记录的豚鼠心室细胞,来研究几何不对称性对动作电位传播的影响。LR细胞模型与记录的真实细胞动作电位的总体对应性相当好,真实细胞和LR模型细胞的强度 - 持续时间曲线总体上相符。实验方案使我们能够改变模拟模型或真实细胞的有效大小。1)当我们将真实细胞大小归一化为LR模型细胞大小时,模型细胞与真实细胞之间传播所需的电导大于两个LR模型细胞之间传导所需的电导(5.4纳秒),当我们刺激LR模型细胞时(8.3±0.6纳秒)的差异比刺激真实细胞时(7.0±0.2纳秒)更大。2)即使将真实细胞大小归一化使其等于LR模型细胞大小,真实细胞动作电位波形的电负荷仍大于LR模型细胞。3)当跟随细胞的大小加倍时,传播所需的电导会显著增加;但这种增加在从真实细胞到LR模型细胞的传导中最大,从LR模型细胞到真实细胞的传导中较小,从LR模型细胞到LR模型细胞的传导中最小。这种“模型钳制”技术的引入,通过检查由模型细胞和真实心脏细胞组成的细胞对传导的对称性,使得能够在极端耦合条件下根据其源 - 汇行为来测试所提出的心脏细胞膜模型。我们将这项技术的实验工作重点放在了可能导致传导阻滞的极端解耦情况上。此外,分析决定传导成败的几何因素对于理解心肌梗死中发生的不连续传导过程很重要。