A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates
A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates
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DOI：
10.1529/biophysj.106.98160
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发表时间：
2008-01-15
影响因子：
3.4
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
--
作者：
Mahajan, Aman;Shiferaw, Yohannes;Weiss, James N.
心脏动作电位的数学建模已被证明是阐明心脏功能的各个方面的强大工具，包括心律失常。然而，目前还没有一个详细的动作电位模型能准确地再现与室性心动过速和纤颤相关的快速心率下心脏动作电位和细胞内钙(Ca-i)循环的动力学。这项研究的目的就是开发这样一个模型。利用已有的兔心室肌动作电位模型，我们根据在35-37℃下获得的新的膜片钳实验数据，对L型钙电流(I-Ca，I-L)和CaI循环公式进行了修正，采用了35-37℃的穿孔膜片构型。新模型结合了最小的七态马尔可夫钙模型，结合我们先前发表的动态钙-I循环模型，再现了实验观察到的动作电位时程和钙-I瞬变交替。并准确再现动态起搏或S1S2起搏获得的实验动作电位时程恢复曲线。
Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca-i) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I-Ca,I-L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I-Ca,I-L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca-i cycling model, the new model replicates experimentally observed action potential duration and Ca-i transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.