Ionic mechanism of electrical alternans
Ionic mechanism of electrical alternans
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DOI：
10.1152/ajpheart.00612.2001
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发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Gilmour, RF
中科院分区：
文献类型：
--
作者：
Fox, JJ;McHarg, JL;Gilmour, RF
虽然动作电位持续时间交替（APD）是快速节奏的犬心室的一个强大特征，但目前可用的心肌细胞离子模型并不能重现这一现象。为了解决这个问题，我们根据以前的模型和最近的实验数据开发了一个新的离子模型，使用电流的公式。与现有模型相比，在去极化电位下，内向整流器K+电流（I-K1）减小，延迟整流器K+电流（I-Kr）快速分量的最大电导和整流增大，I-Kr激活动力学减慢。延迟整流器的慢速部分K+电流（I-Ks）的幅度增加，激活转移到较低的正电压，而l型Ca2+电流（I-Ca）被修改以产生更小，更快速的灭活电流。最后，采用细胞内钙动力学的简化形式。在该模型中，APD交替发生在周期长度= 150 ~ 210 ms，最大交替幅度为39 ms。通过降低I-Ca量或钙诱导的失活量以及增加I-K1、I-Kr或I-Ks的量来抑制APD交替。这些结果为APD替代物建立了离子基础，这将促进消除替代物的药理学方法的发展。
Although alternans of action potential duration (APD) is a robust feature of the rapidly paced canine ventricle, currently available ionic models of cardiac myocytes do not recreate this phenomenon. To address this problem, we developed a new ionic model using formulations of currents based on previous models and recent experimental data. Compared with existing models, the inward rectifier K+ current (I-K1) was decreased at depolarized potentials, the maximum conductance and rectification of the rapid component of the delayed rectifier K+ current (I-Kr) were increased, and I-Kr activation kinetics were slowed. The slow component of the delayed rectifier K+ current (I-Ks) was increased in magnitude and activation shifted to less positive voltages, and the L-type Ca2+ current (I-Ca) was modified to produce a smaller, more rapidly inactivating current. Finally, a simplified form of intracellular calcium dynamics was adopted. In this model, APD alternans occurred at cycle lengths = 150-210 ms, with a maximum alternans amplitude of 39 ms. APD alternans was suppressed by decreasing I-Ca magnitude or calcium-induced inactivation and by increasing the magnitude of I-K1, I-Kr, or I-Ks. These results establish an ionic basis for APD alternans, which should facilitate the development of pharmacological approaches to eliminating alternans.