Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model
Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model
复制标题
DOI：
10.1152/ajpheart.01298.2007
复制
发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Henriquez, Craig S.
中科院分区：
文献类型：
--
作者：
Jacquemet, Vincent;Henriquez, Craig S.
存在于心肌内的大量非肌细胞可以通过间隙连接与肌细胞建立电连接，这种连接是自然形成的或作为细胞治疗的结果。耦合的强度及其对动作电位特性和传导的潜在影响尚不清楚。本研究使用计算机模拟来研究肌细胞与成纤维细胞偶联的负载诱导的电生理后果，其中成纤维细胞的静息电位、密度、分布和偶联强度是不同的。传导速度（CV）、上冲程速度和动作电位持续时间（APD）在二维微结构组织模型中对纵向和横向脉冲传播进行了分析，该模型用于表示被成纤维细胞层覆盖的单层心肌细胞培养。结果表明：1)在弱耦合（8 nS）下，所有效应均达到饱和；4) 90%复极时APD通过与成纤维细胞的偶联延长0 ~ 20 ms（高成纤维细胞密度和偶联可延长60 ~ 80 ms）。APD的变化依赖于成纤维细胞静息电位。成纤维细胞和肌细胞的这种复杂的、偶联依赖的相互作用也与心脏中其他非肌细胞的整合有关，例如那些用于细胞治疗的非肌细胞。
The numerous nonmyocytes present within the myocardium may establish electrical connections with myocytes through gap junctions, formed naturally or as a result of a cell therapy. The strength of the coupling and its potential impact on action potential characteristics and conduction are not well understood. This study used computer simulation to investigate the load-induced electrophysiological consequences of the coupling of myocytes with fibroblasts, where the fibroblast resting potential, density, distribution, and coupling strength were varied. Conduction velocity (CV), upstroke velocity, and action potential duration (APD) were analyzed for longitudinal and transverse impulse propagation in a two-dimensional microstructure tissue model, developed to represent a monolayer culture of cardiac cells covered by a layer of fibroblasts. The results show that 1) at weak coupling ( 8 nS), all of the effects saturated; and 4) APD at 90% repolarization was usually prolonged by 0-20 ms (up to 60-80 ms for high fibroblast density and coupling) by the coupling to fibroblasts. The changes in APD depended on the fibroblast resting potential. This complex, coupling-dependent interaction of fibroblast and myocytes also has relevance to the integration of other nonmyocytes in the heart, such as those used in cellular therapies.