Electrotonic Coupling between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization
Electrotonic Coupling between Human Atrial Myocytes and Fibroblasts Alters Myocyte Excitability and Repolarization
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DOI：
10.1016/j.bpj.2009.07.054
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发表时间：
2009-10-21
影响因子：
3.4
通讯作者：
Trayanova, Natalia A.
中科院分区：
文献类型：
--
作者：
Maleckar, Mary M.;Greenstein, Joseph L.;Trayanova, Natalia A.
心房纤维化与心律不齐的发育和维持有关，其特征是细胞外基质的扩展和成纤维细胞数量增加（FBS）。心肌细胞和FBS之间的电子耦合可能有助于心律失常基质的形成。但是，这些细胞 - 细胞相互作用在正常和患病心房的功能中的作用仍然很少了解。这项研究的目的是获得机械洞察力的洞察力，以了解电量FB-肌细胞偶联对心肌细胞兴奋性和复极化的作用。为了代表系统，人类心肌细胞（HAM）耦合到可变数量的FBS，我们采用了HAM的新离子模型，以及用于心房FBS的各种膜表示。模拟阐明了改变细胞间耦合电导，电生理FB特性以及刺激速率对心肌细胞动作电位的影响。结果表明，肌细胞静止电位和动作电位波形由耦合FBS的性质和数量，耦合程度和起搏频率强烈调节。我们的模型提供了有关异源细胞偶联对HAM电生理学的后果的机械洞察力，并且可以扩展以评估组织和器官水平的这些含义。
Atrial fibrosis has been implicated in the development and maintenance of atrial arrhythmias, and is characterized by expansion of the extracellular matrix and an increased number of fibroblasts (Fbs). Electrotonic coupling between atrial myocytes and Fbs may contribute to the formation of an arrhythmogenic substrate. However, the role of these cell-cell interactions in the function of both normal and diseased atria remains poorly understood. The goal of this study was to gain mechanistic insight into the role of electrotonic Fb-myocyte coupling on myocyte excitability and repolarization. To represent the system, a human atrial myocyte (hAM) coupled to a variable number of Fbs, we employed a new ionic model of the hAM, and a variety of membrane representations for atrial Fbs. Simulations elucidated the effects of altering the intercellular coupling conductance, electrophysiological Fb properties, and stimulation rate on the myocyte action potential. The results demonstrate that the myocyte resting potential and action potential waveform are modulated strongly by the properties and number of coupled Fbs, the degree of coupling, and the pacing frequency. Our model provides mechanistic insight into the consequences of heterologous cell coupling on hAM electrophysiology, and can be extended to evaluate these implications at both tissue and organ levels.