Development of novel mathematical models for human cardiac myocytes based on bifurcation analysis and comparative study

基于分叉分析和比较研究的人类心肌细胞新数学模型的开发

• 批准号: 23590266
• 负责人: KURATA Yasutaka
• 金额: $ 3.24万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590266/
• 关键词: システム生理; フィジオーム; ヒト心筋モデル; 分岐解析; システム生理学; 非線形力学; 分岐理論; 生物・生体工学; 生物物理; 生理学

The aim of this study was to develop novel mathematical models for human cardiac myocytes which can well reproduce experimental data and are suitable for mathematical analyses. We first constructed the database of previous mathematical models of human and animal cardiac myocytes for model development. Based on the database, we have developed novel human ventricular and atrial myocyte models which are improved versions of previous models. To develop Purkinje and sinoatrial node cell models, we further compared the experimental data on expression of ion channels in individual cell types. Novel Purkinje and sinoatrial node cell models have been developed by parameter adjustment according to the the expression data and by analyzing bifurcation structures during inhibition of the inward-rectifier potassium channel current and incorporation of the hyperpolarization-activated cation channel current. These novel model cells are useful as modules for development of human heart models.

本研究的目的是为人类心肌细胞开发新的数学模型，该模型可以很好地重现实验数据并适合数学分析。我们首先构建了人类和动物心肌细胞先前数学模型的数据库以用于模型开发。基于该数据库，我们开发了新型人类心室和心房肌细胞模型，该模型是先前模型的改进版本。为了开发浦肯野细胞和窦房结细胞模型，我们进一步比较了各个细胞类型中离子通道表达的实验数据。通过根据表达数据调整参数并分析抑制内向整流钾通道电流和掺入超极化激活的阳离子通道电流期间的分叉结构，开发了新型浦肯野细胞和窦房结细胞模型。这些新颖的模型细胞可用作开发人类心脏模型的模块。

项目成果

Roles of sarcoplasmic reticulum Ca^2+ clock and Na^+/Ca^2+ exchanger in sinoatrial node pacemaking : Insights from bifurcation analysis of mathematical models(Intracellular Ca clock and cell excitation)

肌浆网Ca^2时钟和Na^/Ca^2交换器在窦房结起搏中的作用：数学模型分叉分析的见解（细胞内Ca时钟和细胞激发）

• 发表时间: 2012
• 作者: Kurata Y;Hisatome I;Shibamoto T
• 通讯作者: Shibamoto T

Effect of hyperpolarization-activated current If on robustness of sinoatrial node pacemaking: theoretical study on influence of intracellular Na+ concentration

• DOI: 10.1152/ajpheart.00777.2012
• 发表时间: 2013-05-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Kurata, Yasutaka;Hisatome, Ichiro;Shibamoto, Toshishige
• 通讯作者: Shibamoto, Toshishige

Effect of hyperpolarization-activated current I_f on robustness of sinoatrial node pacemaking : theoretical study in connection with intracellular Na^+ concentration changes

超极化激活电流 I_f 对窦房结起搏稳健性的影响：与细胞内 Na^ 浓度变化相关的理论研究

• 发表时间: 2013
• 作者: Kurata Y;Hisatome I;Shibamoto T
• 通讯作者: Shibamoto T

過分極活性化陽イオンチャネル電流の洞結節細胞ロバスト性への影響:モデル細胞の分岐構造解析による理論的検証

超极化激活的阳离子通道电流对窦房结细胞稳健性的影响：模型细胞分支结构分析的理论验证

• 发表时间: 2012
• 作者: 倉田康孝;久留一郎;芝本利重
• 通讯作者: 芝本利重

Dynamical mechanisms of early afterdepolarizations in long QT syndromes : insights from bifurcation analysis of mathematical models for human ventricular myocytes

长QT综合征早期后除极的动力学机制：人类心室肌细胞数学模型分叉分析的见解

• 发表时间: 2014
• 作者: Kurata Y;Hisatome I;Tanida M;Shibamoto T
• 通讯作者: Shibamoto T