REENTRANT ACTIVITY IN CULTURED CARDIAC CELL MONOLAYERS
培养的心肌细胞单层中的重入活性
基本信息
- 批准号:6558853
- 负责人:
- 金额:$ 6.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-08-08 至 2005-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Reentrant mechanisms play a primary role in many types of arrhythmias, including tachycardia and flutter in the atria, ventricles, and atrioventricular node. Reentry may involve anatomical pathways, or it may be functional, with leading circle, figure-eight, anisotropic, and spiral wave variants. The primary goal of this research is to establish a simple and reproducible cultured cell model for the study of anatomical and functional cardiac reentry under well-controlled experimental conditions. We propose to use voltage-sensitive dyes and high- resolution optical mapping to monitor reentrant activity in monolayers of neonatal rat heart cells. A detailed computational model will be verified against experimental data drawn from action potential and intracellular calcium measurements, and their restitution and rate-dependent behavior in this experimental model. The computational model will be used to identify the ionic currents and biophysical mechanisms responsible for reentry behavior. New microfabrication and surface chemical approaches will also be used to develop patterned substrates that direct the growth of cells in the monolayers. The combined experimental and computational approach that is proposed in this study will permit a detailed quantitative analysis and dissection of tissue behavior down to the cellular level. We will, 1) formulate an experimentally-based, biophysical model of the neonatal rat cardiac cell monolayer 2) characterize reentry in confluent monolayers of cultured neonatal rat heart cells, and 3) determine the electrophysiological properties and role of the core of the reentrant circuits. Issues of critical mass, excitable gap, and leading circle vs. spiral wave reentry will be addressed. These aims will establish the cultured cell monolayer as a well-controlled, versatile and quantitative experimental model for basic studies of reentry- based arrhythmias. The simplicity and flexibility of this model system provides numerous advantages over existing tissue models of reentrant arrhythmia. Moreover, the cell culture is well suited for studies involving pharmacological, genetic and molecular manipulation.
折返机制在许多类型的心律失常中起主要作用,包括心动过速和房室、房室结的扑动。重返大气层可能涉及解剖路径,也可能是功能性的,有前导圆波、八字波、各向异性波和螺旋波。本研究的主要目的是建立一种简单、可重复性的培养细胞模型,用于在良好控制的实验条件下研究解剖和功能的心脏折返。我们建议使用电压敏感染料和高分辨率光学映射来监测新生大鼠心肌细胞单层折返活动。在这个实验模型中,一个详细的计算模型将根据来自动作电位和细胞内钙测量的实验数据进行验证,以及它们的恢复和速率依赖行为。计算模型将用于确定导致再入行为的离子电流和生物物理机制。还将使用新的微制造和表面化学方法来开发图案化的衬底,以指导单层中细胞的生长。这项研究中提出的实验和计算相结合的方法将允许对组织行为进行详细的量化分析和剖析,直到细胞水平。我们将,1)建立一个基于实验的新生大鼠心肌细胞单层生物物理模型,2)表征培养的新生大鼠心肌细胞融合单层中的折返,以及3)确定折返回路核心的电生理特性和作用。将讨论临界质量、可激发间隙和前导圆与螺旋波再入的问题。这些目标将使培养的细胞单层成为一个控制良好的、通用的、定量的实验模型,用于基础研究基于再入的心律失常。与现有的折返性心律失常组织模型相比,该模型系统的简单性和灵活性提供了许多优势。此外,细胞培养非常适合于涉及药理、遗传和分子操作的研究。
项目成果
期刊论文数量(0)
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