Kohl P, Day K, Noble D
University Laboratory of Physiology, University of Oxford, United Kingdom.
Can J Cardiol. 1998 Jan;14(1):111-9.
Cardiac mechanical and electrical activity are closely interrelated. While excitation-contraction coupling is rather well characterized, less is known about cellular mechanisms that promote mechanically induced changes in cardiac electrical activity--mechano-electric feedback.
To integrate experimental findings on stretch activation of ion channels and length-dependent changes in intracellular calcium handling into a mathematical description of cardiac cellular activity.
Simulations are based on the cellular OXSOFT HEART v4.8 models of electrical activity of single cardiac cells of different populations and species. Sarcolemmal stretch-activated channels, mechanically induced changes in the affinity of troponin C to calcium, and length-dependent modulation of calcium handling by the sarcoplasmic reticulum were introduced into the models and linked to a description of sarcomere length or isometric tension.
Transient or sustained stretch of cardiomyocytes was simulated during electrical systole and diastole. The electrophysiological response observed in the model depended on timing and severity of mechanical stimulation and on the main subcellular target of the intervention. Responses ranged from triggering of premature action potentials, over changes in action potential shape and duration, to length-dependent variations in contractile behaviour. Modelling findings could be related to experimental observations and may help to explain some of the contradictory data in the literature. The model is sufficiently complete to reproduce experimental findings and to help identify causally linked events.
心脏的机械活动和电活动密切相关。虽然兴奋-收缩偶联已得到较好的描述，但对于促进心脏电活动中机械诱导变化的细胞机制——机械电反馈，人们了解较少。
将离子通道拉伸激活和细胞内钙处理长度依赖性变化的实验结果整合到心脏细胞活动的数学描述中。
模拟基于不同群体和物种的单个心脏细胞电活动的细胞OXSOFT HEART v4.8模型。将肌膜拉伸激活通道、机械诱导的肌钙蛋白C对钙亲和力的变化以及肌浆网对钙处理的长度依赖性调节引入模型，并与肌节长度或等长张力的描述相关联。
在电收缩期和舒张期模拟了心肌细胞的短暂或持续拉伸。模型中观察到的电生理反应取决于机械刺激的时间和强度以及干预的主要亚细胞靶点。反应范围从触发过早动作电位、动作电位形状和持续时间的变化到收缩行为的长度依赖性变化。建模结果可能与实验观察结果相关，有助于解释文献中的一些矛盾数据。该模型足够完整，能够重现实验结果并有助于识别因果相关事件。
