title: An integrated finite element simulation of cardiomyocyte function based on triphasic theory.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, School of Engineering, The University of Tokyo Tokyo, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Hatano
authors.affiliation: Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo Chiba, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Okada
authors.affiliation: Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo Chiba, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Washio
authors.affiliation: Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo Chiba, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hisada
authors.affiliation: Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo Chiba, Japan.
authors.forename: Seiryo
authors.initials: S
authors.lastname: Sugiura
keywords: cardiomyocyte; finite element method; mitochondria; t-tubule; triphasic theory