ヒト心筋細胞数理モデルの開発

It is inevitable to examine drug effects on electrical activities as well as mechanical functions of human heart during drug development. Generally, drug assessments in human can only be executed at a late stage of drug development, and we predict drug effects on human by extrapolating data from animal experiments. In this process, a mathematical model of human cardiac cell, which enables us to conduct virtual experiments using computer, will be a useful tool. So far, several types of human cardiac cell models are available for membrane excitation, and only one Excitation-Contraction (E-C) coupling model was published by Sachse et al (2003). Therefore, we started developing a comprehensive model of human cardiac cell. We developed a human models of fast Na, L-type Ca, transient outward, delayed rectifier K currents and a contraction model based on the experimental data from intact human cardiac myocytes, although which was limited in comparison with animal data. Then, we incorporated the human models into a comprehensive cell model of guinea-pig heart, the Kyoto model (Takeuchi et al., 2006) to compose a cell model of human heart. We succeeded in construction of the human cardiac cell model which well reproduces E-C coupling. This novel human cardiac cell model will illustrate how we can extrapolate data from animal experiments to human response. [J Physiol Sci. 2007;57 Suppl:S202]