A mathematical model of electrotonic interactions between ventricular myocytes and fibroblasts
A mathematical model of electrotonic interactions between ventricular myocytes and fibroblasts
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DOI：
10.1529/biophysj.106.101410
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Giles, Wayne R.
中科院分区：
文献类型：
--
作者：
MacCannell, K. Andrew;Bazzazi, Hojjat;Giles, Wayne R.
功能性细胞间偶联已在心脏成纤维细胞网络以及成纤维细胞与心房或心室肌细胞之间得到证实。在这项研究中，通过实施人类心室动作电位的十个Tusscher模型，并将其与哺乳动物心室成纤维细胞的电生理模型相结合，研究了这些相互作用的后果。我们的模拟揭示了1和4个成纤维细胞与单个心室肌细胞耦合的显著电生理后果。这些变化包括平台高度和/或动作电位持续时间（APD）的变化以及潜在离子电流的变化。进行了两组模拟。首先，将成纤维细胞建模为一个球形细胞，其电容为6.3 pF，欧姆膜电阻为10.7 G ω。当这些“被动”成纤维细胞与肌细胞结合时，它们引起APD的轻微延长，但平台、放电阈值或初始去极化速率没有变化。相比之下，当加入成纤维细胞中表达的时间和电压门控K+电流后，同样的肌细胞-成纤维细胞复合物模型时，观察到更明显的效果：动作电位的平台高度降低，APD明显缩短。此外，每个成纤维细胞对每个肌细胞的动作电位都表现出显著的电张力去极化，成纤维细胞的静息电位与偶联心室肌细胞的静息电位非常接近。
Functional intercellular coupling has been demonstrated among networks of cardiac fibroblasts, as well as between fibroblasts and atrial or ventricular myocytes. In this study, the consequences of these interactions were examined by implementing the ten Tusscher model of the human ventricular action potential, and coupling it to our electrophysiological models for mammalian ventricular fibroblasts. Our simulations reveal significant electrophysiological consequences of coupling between 1 and 4 fibroblasts to a single ventricular myocyte. These include alterations in plateau height and/or action potential duration (APD) and changes in underlying ionic currents. Two series of simulations were carried out. First, fibroblasts were modeled as a spherical cell with a capacitance of 6.3 pF and an ohmic membrane resistance of 10.7 G Omega. When these "passive'' fibroblasts were coupled to a myocyte, they caused slight prolongation of APD with no changes in the plateau, threshold for firing, or rate of initial depolarization. In contrast, when the same myocyte-fibroblast complexes were modeled after addition of the time- and voltage-gated K+ currents that are expressed in fibroblasts, much more pronounced effects were observed: the plateau height of the action potential was reduced and the APD shortened significantly. In addition, each fibroblast exhibited significant electrotonic depolarizations in response to each myocyte action potential and the resting potential of the fibroblasts closely approximated the resting potential of the coupled ventricular myocyte.