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1 CREST of JST, Kawaguchi-shi, Saitama, Japan; Graduate School of Frontier Sciences, The Universtiy of Tokyo, Tokyo, Japan
2 Graduate School of Frontier Sciences, The Universtiy of Tokyo, Tokyo, Japan
3 Graduate School of Medicine, The Universtiy of Tokyo, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: okada{at}sml.k.u-tokyo.ac.jp.
In order to investigate the characteristics and underlying mechanisms of Ca2+ wave propagation, we developed a 3D 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 calcium-induced calcium release were the basic mechanisms, but use of the finite element method enabled us to simulate not only the wave propagation in 3D 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 (TnC) 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 3D 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.
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