PROJECT II

该项目致力于开发一种跨生物层次的可扩展性的“自下而上”的观点 从细胞到组织的组织。为此，我们重点研究肌细胞如何相互作用以产生 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会导致 细胞内钙离子浓度([Ca~(2+)]i)和收缩是由于Ca~(2+)离子与肌丝结合所致。 然而，[Ca~(2+)]i的变化可以影响负责激发的离子电流，从而改变 电信号。此外，器官水平上的最佳收缩顺序不仅需要信号 还包括细胞间信号的有效传输。因此，心脏的跳动 关键取决于监管互动和反馈循环，这是纽约证交所的共同主题。 因为像缺血和心力衰竭这样的病理现象与心脏的紊乱有关 电信号和钙信号之间的耦合，更好地描述了细胞内的这些环路 组织水平将提高我们对心脏病的理解，并提出治疗心脏病的新靶点 治疗。

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.