Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium.
Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium.
复制标题
DOI：
10.1016/j.pbiomolbio.2009.01.010
复制
发表时间：
2008-10
影响因子：
3.8
通讯作者：
Giles WR
中科院分区：
文献类型：
--
作者：
Maleckar MM;Greenstein JL;Trayanova NA;Giles WR
在哺乳动物心脏中，肌细胞和成纤维细胞可以通过间隙连接或连接蛋白介导的电流进行通信。本文详细分析了这种电紧张耦合对人心室肌细胞动作电位波形的影响。本研究采用了最近开发的人类心房肌细胞的数学模型，探讨这种异质性细胞间相互作用对人类心房动作电位的后果。两个独立的生理过程，改变人体心房的生理进行了研究。i）通过在心房肌细胞的数学模型中包括时间无关的乙酰胆碱激活的K+电流，研究了自主神经递质乙酰胆碱对心房动作电位的影响。ii）由利钠肽激活的非选择性阳离子电流已被并入先前发表的心脏成纤维细胞的数学模型中。这些结果确定了乙酰胆碱的微妙影响，这是由人心房肌细胞中离子电流之间的非线性相互作用引起的。它们还说明了当利钠肽介导的阳离子电导被激活时，成纤维细胞-肌细胞源-汇原理引起的动作电位波形的显著改变。额外的计算还说明了心房心肌内这两种细胞类型特异性电导的同时激活的影响。这项研究提供了一个基础，开始评估数学建模的效用，了解详细的细胞间的相互作用内的复杂的旁分泌环境的人心房心肌。
In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electrotonic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell–cell interaction on the action potential of the human atrium. Two independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic transmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K+ current in this mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a previously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear interactions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibroblast–myocyte source–sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effects of simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to assess the utility of mathematical modeling in understanding detailed cell–cell interactions within the complex paracrine environment of the human atrial myocardium.
登录
查看更多内容
影响因子：
5.5
作者：
Gaborit, Nathalie;Le Bouter, Sabrina;Demolombe, Sophie
通讯作者：
Demolombe, Sophie
影响因子：
--
作者：
FERMINI, B;WANG, Z;NATTEL, S
通讯作者：
NATTEL, S
影响因子：
4.8
作者：
Horio, T;Tokudome, T;Kangawa, K
通讯作者：
Kangawa, K
影响因子：
20.1
作者：
Gaudesius, G;Miragoli, M;Rohr, S
通讯作者：
Rohr, S
影响因子：
37.8
作者：
Dobrev, D;Graf, E;Ravens, U
通讯作者：
Ravens, U