New Mathematical Models for the Mouse Atrial Fast Sodium Channel

Shanzhuo Zhang, Wei Wang, Kuanquan Wang, Henggui Zhang
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Abstract

The fast sodium channel (FSC) is one of the most important channels in the cardiomyocytes. It leads the activation of the cardiac action potentials and its dysfunction may leads to many severe pathologies. However, the currently widely used FSC model is not developed for mouse, and relatively outdated compared with the emerging experimental data on mouse atria, making the model less reliable in investigating the mechanisms underlying atrial arrhythmias. In this work, we intend to develop a new model for the mouse atrial FSC which can reproduce the newly published experimental data. The kinetics of and the current generated by our new model were thoroughly validated. We investigated the response of the new model to infra- or supra-threshold stimuli and found that it needs a smaller stimulus to be activated and has a higher driving ability compared with the old model. The current amplitude of the new model also shows a smoother stimulus-dependent curve than the old model. This model will be a more suitable tool in the research of atrial arrhythmias.
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小鼠心房快速钠通道的新数学模型
快速钠离子通道(FSC)是心肌细胞中最重要的通道之一。它导致心脏动作电位的激活,其功能障碍可导致许多严重的病理。然而,目前广泛使用的FSC模型并不是针对小鼠开发的,与新兴的小鼠心房实验数据相比,FSC模型相对过时,使得该模型在研究心房心律失常的机制方面不太可靠。在这项工作中,我们打算建立一个新的小鼠心房FSC模型,可以复制新发表的实验数据。我们的新模型产生的动力学和电流得到了彻底的验证。我们研究了新模型对阈下或阈上刺激的反应,发现与旧模型相比,它需要更小的刺激才能被激活,并且具有更高的驾驶能力。新模型的当前振幅也显示出比旧模型更平滑的刺激依赖曲线。该模型将成为研究心房心律失常的一个更合适的工具。
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