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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Three-dimensional simulation of calcium waves and contraction in cardiomyocytes using the finite element method

¹Core Research for Evolutional Science and Technology of the Japan Science and Technology Agency, Saitama; ²Computational Biomechanics Division, Institute of Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo; and ³Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Submitted 1 June 2004 ; accepted in final form 15 October 2004

To investigate the characteristics and underlying mechanisms of Ca²⁺ wave propagation, we developed a three-dimensional (3-D) simulator of cardiac myocytes, in which the sarcolemma, myofibril, and Z-line structure with Ca²⁺ release sites were modeled as separate structures using the finite element method. Similarly to previous studies, we assumed that Ca²⁺ diffusion from one release site to another and Ca²⁺-induced Ca²⁺ release were the basic mechanisms, but use of the finite element method enabled us to simulate not only the wave propagation in 3-D space but also the active shortening of the myocytes. Therefore, in addition to the dependence of the Ca²⁺ wave propagation velocity on the sarcoplasmic reticulum Ca²⁺ content and affinity of troponin C for Ca²⁺, we were able to evaluate the influence of active shortening on the propagation velocity. Furthermore, if the initial Ca²⁺ release took place in the proximity of the nucleus, spiral Ca²⁺ waves evolved and spread in a complex manner, suggesting that this phenomenon has the potential for arrhythmogenicity. The present 3-D simulator, with its ability to study the interaction between Ca²⁺ waves and contraction, will serve as a useful tool for studying the mechanism of this complex phenomenon.

cardiac muscle cell; excitation-contraction coupling; mechanoelectrical feedback; spiral wave; arrhythmia