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

To investigate the characteristics and underlying mechanisms of Ca(2+) wave propagation, we developed a three-dimensional (3-D) simulator of cardiac myocytes, in which the sarcolemma, myofibril, and Z-line structure with Ca(2+) release sites were modeled as separate structures using the finite element method. Similarly to previous studies, we assumed that Ca(2+) diffusion from one release site to another and Ca(2+)-induced Ca(2+) 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 Ca(2+) wave propagation velocity on the sarcoplasmic reticulum Ca(2+) content and affinity of troponin C for Ca(2+), we were able to evaluate the influence of active shortening on the propagation velocity. Furthermore, if the initial Ca(2+) release took place in the proximity of the nucleus, spiral Ca(2+) 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 Ca(2+) waves and contraction, will serve as a useful tool for studying the mechanism of this complex phenomenon.