Hatano Asuka, Okada Jun-Ichi, Washio Takumi, Hisada Toshiaki, Sugiura Seiryo
Department of Mechanical Engineering, School of Engineering, The University of Tokyo Tokyo, Japan.
Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo Chiba, Japan.
Front Physiol. 2015 Oct 20;6:287. doi: 10.3389/fphys.2015.00287. eCollection 2015.
In numerical simulations of cardiac excitation-contraction coupling, the intracellular potential distribution and mobility of cytosol and ions have been mostly ignored. Although the intracellular potential gradient is small, during depolarization it can be a significant driving force for ion movement, and is comparable to diffusion in terms of net flux. Furthermore, fluid in the t-tubules is thought to advect ions to facilitate their exchange with the extracellular space. We extend our previous finite element model that was based on triphasic theory to examine the significance of these factors in cardiac physiology. Triphasic theory allows us to study the behavior of solids (proteins), fluids (cytosol) and ions governed by mechanics and electrochemistry in detailed subcellular structures, including myofibrils, mitochondria, the sarcoplasmic reticulum, membranes, and t-tubules. Our simulation results predicted an electrical potential gradient inside the t-tubules at the onset of depolarization, which corresponded to the Na(+) channel distribution therein. Ejection and suction of fluid between the t-tubules and the extracellular compartment during isometric contraction were observed. We also examined the influence of t-tubule morphology and mitochondrial location on the electrophysiology and mechanics of the cardiomyocyte. Our results confirm that the t-tubule structure is important for synchrony of Ca(2+) release, and suggest that mitochondria in the sub-sarcolemmal region might serve to cancel Ca(2+) inflow through surface sarcolemma, thereby maintaining the intracellular Ca(2+) environment in equilibrium.
在心脏兴奋 - 收缩偶联的数值模拟中，细胞内电位分布以及胞质溶胶和离子的流动性大多被忽略。尽管细胞内电位梯度很小，但在去极化过程中，它可能是离子移动的重要驱动力，并且在净通量方面与扩散相当。此外，横管中的液体被认为可平流输送离子，以促进其与细胞外空间的交换。我们扩展了先前基于三相理论的有限元模型，以研究这些因素在心脏生理学中的重要性。三相理论使我们能够在详细的亚细胞结构中研究受力学和电化学支配的固体（蛋白质）、流体（胞质溶胶）和离子的行为，这些亚细胞结构包括肌原纤维、线粒体、肌浆网、膜和横管。我们的模拟结果预测，在去极化开始时横管内部存在电位梯度，这与其中的钠通道分布相对应。观察到在等长收缩期间横管与细胞外间隙之间的液体排出和吸入。我们还研究了横管形态和线粒体位置对心肌细胞电生理学和力学的影响。我们的结果证实，横管结构对于钙释放的同步性很重要，并表明肌膜下区域的线粒体可能有助于抵消通过表面肌膜的钙流入，从而维持细胞内钙环境的平衡。
