STUDY OF CARDIAC ARRHYTHMIAS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目的目标是利用连接在多细胞组织中的复杂心肌细胞模型来研究心律失常的机制。心律失常的起因可能是长QT综合征、钙离子处理功能障碍或心脏组织电导率降低。心律失常可导致室颤和心脏性猝死。最近，我们在PSC的GRANT(MCB010020P)的帮助下，建立了包含15个离子电流和转运体的小鼠心肌细胞动作电位模型和先进的钙离子处理系统。该模型重现了主要离子电流、负责心肌细胞收缩的钙离子通量和动作电位的电压钳实验。该模型将用于模拟多细胞心脏组织中动作电位的产生和传播。非线性动力学和混沌理论的方法将被用来阐明心律失常的产生机制，这是由于负责IKto、IKUR或细胞间连接的离子通道的遗传突变(连接蛋白43)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is the study of mechanisms of cardiac arrhythmias with complex cardiac cell model connected in multicellular tissue. The origin of cardiac arrhythmia can be long QT syndrome, dysfunction of Ca2+ handling, or reduced conductivity of heart tissue. The cardiac arrhythmia can lead to ventricular fibrillation and sudden cardiac death. Recently we developed a model of action potential for mouse cardiac ventricular myocyte that includes 15 ionic currents and transporters and advanced Ca2+ handling system with the help of the Grant from PSC (MCB010020P). The model reproduced voltage-clamp experiments on major ionic currents, Ca2+ fluxes responsible for the myocyte contraction, and action potential. This model will be used in this project for simulation of action potential generation and propagation in multicellular cardiac tissue. Methods of nonlinear dynamics and chaos theory will be used to elucidate mechanisms of arrhythmia generation because of genetic mutations in ion channels responsible for IKto, IKur, or intercellular connections (Connexin43).