An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes
An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes
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DOI：
10.1016/j.eupc.2005.03.019
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发表时间：
2005-09-01
期刊：
影响因子：
6.1
通讯作者：
McCulloch, AD
中科院分区：
文献类型：
--
作者：
Healy, SN;McCulloch, AD
目的建立符合实验观察的兔心室肌细胞拉伸激活和拉伸调节电流的离子模型，用于研究这些电流在完整心肌中的作用。方法和结果将非特异性阳离子选择性拉伸激活电流Ins引入心外膜、心内膜和心肌中心室肌细胞Puglisi-Bers离子模型。利用该模型，我们预测在20%复极时动作电位持续时间（APD）和动作电位幅度减少，静息跨膜电位升高，APD增加或减少（90），这取决于I-ns的逆转电位。拉伸引起的I-K1降低（70%），加上一个小的I-ns电流（g(ns) = 10 pS），导致APD降低（20）和APD增加（90），并降低了传导的安全系数。增加I-K1（150%）加上较大的Ins电流（g(ns)=40 pS），也会导致APD20降低，APD增加（90），但安全系数更高。心内膜和心肌中间的细胞似乎对拉伸引起的动作电位变化最敏感。添加K+特异性拉伸激活电流（SAC） IKO导致动作电位缩短。结论IK1的跨壁异质性可降低完整心肌内禀离子通道密度、非均匀应变和电紧张效应引起的复极化梯度。(c) 2005年欧洲心脏病学会。Elsevier Ltd.出版。版权所有。
Aims To develop an ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes consistent with experimental observations, that can be used to investigate the role of these currents in intact myocardium.Methods and results A non-specific cation-selective stretch-activated current Ins, was incorporated into the Puglisi-Bers ionic model of epicardial, endocardial and midmyocardial ventricular myocytes. Using the model, we predict a reduction in action potential duration at 20% repolarization (APD(20)) and action potential amplitude, an elevated resting transmembrane potential and either an increase or decrease in APD(90), depending on the reversal potential of I-ns. A stretch-induced decrease in I-K1 (70%), plus a small I-ns current (g(ns) = 10 pS), results in a reduction in APD(20) and increase in APD(90), and a reduced safety factor for conduction. Increasing I-K1 (150%) plus a large Ins current (g(ns)=40 pS), also leads to a reduction in APD20 and increase in APD(90), but with a greater safety factor. Endocardiat and midmyocardial cetts appear to be the most sensitive to stretch-induced changes in action potential. The addition of the K+-specific stretch -activated current (SAC) IKO results in action potential shortening.Conclusion Transmural heterogeneity of IK1 may reduce repolarization gradients in intact myocardium caused by intrinsic ion channel densities, nonuniform strains and electrotonic effects. (c) 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.