PROJECT II

项目二

• 批准号: 7508898
• 负责人: ERIC A SOBIE
• 金额: $ 31.01万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-18 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7508898
• 关键词: Address; Anti-Arrhythmia Agents; Arrhythmia; Behavior; Binding; Biological; Calcium; Cardiac; Cell physiology; Cells; Chemicals; Complex; Computer Analysis; Computer Simulation; Condition; Coupled; Coupling; Dimensions; Disruption; Feedback; Functional disorder; Gene Expression; Heart; Heart Diseases; Heart failure; Hypertrophy; Ions; Ischemia; Link; Localized; Mechanics; Methods; Microfilaments; Modeling; Molecular; Muscle Cells; Myocardium; Neonatal; Organ; Pathology; Pattern; Pharmaceutical Preparations; Phenotype; Physiology; Randomized; Rattus; Research Personnel; Signal Transduction; Simulate; System; Techniques; Tissues; Ventricular; base; case-based; heart cell; heart function; improved; insight; novel; research study; simulation; tool; transcription factor; transmission process

This project is focused on developing a "bottom-up" view of scalability across levels of biological organization from cells to tissue. For this we focus on how myocytes interact with one another to give rise to the electrical activities observed in heart muscle, particularly the pathological activities known as arrhythmias. The mechanical function of the heart is controlled by interactions between electrical and chemical signaling systems. In the simplest representation, electrical excitation in each heart cell leads to an increase in intracellular calcium concentration ([Ca2+]i), and contraction results from Ca2+ ions binding to myofilaments. However, changes in [Ca2+]i can influence the ionic currents responsible for excitation and thereby alter the electrical signal. Moreover, an optimal sequence of contraction at the organ level requires not only signaling within cells but also the effective transmission of signals between cells. Thus, the beating of the heart depends crucially on regulatory interactions and feedback loops, the common themes of the NYCSB. Because pathologies such as ischemia and heart failure are associated with disruptions in the coupling between electrical and Ca2+ signals, a better characterization of these loops at the cellular and tissue levels will improve our understanding of heart disease and suggest novel targets for therapies.

这个项目的重点是开发一个“自下而上”的跨生物学水平的可扩展性视图， 从细胞到组织。为此，我们专注于肌细胞如何相互作用， 在心肌中观察到的电活动，特别是称为心律失常的病理活动。 心脏的机械功能是由电信号和化学信号之间的相互作用控制的 系统.在最简单的表示中，每个心脏细胞中的电兴奋导致心脏细胞中的 细胞内钙浓度（[Ca 2 +]i），收缩由Ca 2+离子结合肌丝引起。 然而，[Ca2+]i的变化可以影响负责激发的离子电流，从而改变细胞内Ca2+浓度。 电信号此外，器官水平的最佳收缩顺序不仅需要信号， 不仅在细胞内，而且在细胞之间有效地传输信号。因此，心脏的跳动 关键取决于监管互动和反馈回路，NYCSB的共同主题。 因为诸如缺血和心力衰竭的病理与心肌细胞的破坏有关， 电信号和Ca2+信号之间的耦合，在细胞内更好地表征这些环， 和组织水平将提高我们对心脏病的理解，并提出新的靶点， 治疗