Calcium Waves in Atrial Cells

心房细胞中的钙波

• 批准号: 6825716
• 负责人: LEIGHTON T. IZU
• 金额: $ 2.69万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-22 至 2005-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825716
• 关键词: atrium; calcium flux; calcium indicator; cardiac myocytes; confocal scanning microscopy; electrophysiology; heart electrical activity; human tissue; laboratory rat; mathematical model; neuromuscular transmission; sarcoplasmic reticulum; supercomputer; tissue /cell culture; video microscopy; voltage /patch clamp; atrium; calcium flux; calcium indicator; cardiac myocytes; confocal scanning microscopy; electrophysiology; heart electrical activity; human tissue; laboratory rat; mathematical model; neuromuscular transmission; sarcoplasmic reticulum; supercomputer; tissue /cell culture; video microscopy; voltage /patch clamp

DESCRIPTION (provided by applicant): This training grant is designed to provide the principal investigator (Pl) with the necessary didactic training and laboratory experience to become an independent biomedical researcher. The PI?s immediate career goals are to acquire the knowledge in using supercomputers and the experimental skills of electrophysiology and microscopy necessary to develop a quantitative understanding of atrial excitation-contraction (E-C) coupling. The Pl?s long-term career goal is to lead a multidisciplinary team of physiologists, mathematicians, physicians, and computer programmers in developing a quantitative understanding of both normal and pathological E-C coupling in atrial cells. Mammalian ventricular cells have an extensive transverse(t)-tubular system that rapidly conducts the action potential from the cell surface to the interior triggering a near synchronous calcium (Ca) release from the sarcoplasmic reticulum (SR) and activation of myofibrils throughout the cell. Atrial cells lack an extensive t-tubular system. How Ca release from the SR far from the cell surface is triggered is unclear. The overall hypothesis is that in atrial cells, Ca entry during an action potential triggers regenerative Ca release from the SR at the cell surface and this regenerative Ca release ("Ca wave") propagates as a wave radially to the center of the cell. The Specific Aims are: (1) Test this hypothesis by correlating atrial single-cell contraction rate and magnitude with the Ca wave?s velocity and amplitude using video rate 2-dimensional confocal microscopy and fluorescent Ca indicators. (2) Develop a mathematical model of the atrial cell Ca control system and solve the model numerically using supercomputers. (3) Evaluate the model by comparing the model?s predictions with experimental measurements of Ca waves in voltage-clamped atrial cells using confocal microscopy. A quantitative model of the atrial Ca control system is necessary for understanding both normal E-C coupling and the origins of pathological spontaneous Ca waves, which recent data suggest can trigger atrial arrhythmias.

描述（由申请人提供）： 该培训补助金旨在为首席研究员（PL）提供 有必要的教学培训和实验室经验 独立的生物医学研究人员。 PI的直接职业目标是 获取使用超级计算机和实验技能的知识 产生定量的必要的电生理学和显微镜 理解心房激发 - 收缩（E-C）耦合。 PL长期 职业目标是领导一个生理学家的多学科团队 数学家，医师和计算机程序员开发 对正常和病理E-C耦合的定量理解 心房细胞。哺乳动物的心室细胞具有广泛的横向（T） - 微型 迅速从细胞中发挥作用电位的系统 表面到内部触发接近同步钙（CA）释放 从肌质网（SR）和整个肌原纤维激活 细胞。心房细胞缺乏广泛的T管系统。如何CA 远离细胞表面的SR释放尚不清楚。这 总体假设是在动作过程中，在心房细胞中，CA进入 潜在的触发会从细胞表面的SR释放再生Ca，并 这种再生Ca释放（“ CA波”）在径向上传播到 细胞中心。具体目的是：（1）通过 将心房单细胞收缩率和大小与CA相关联 使用视频速率二维共焦的波浪速度和振幅 显微镜和荧光CA指标。 （2）开发一个数学模型 心房单元格控制系统并使用数值求解模型 超级计算机。 （3）通过比较模型预测来评估模型 通过对电压斜率的心房细胞中Ca波的实验测量 使用共聚焦显微镜。心房CA控制的定量模型 系统对于理解正常的E-C耦合和起源是必要的 病理自发的CA波，最近的数据表明可以触发这一点 心律不齐。