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

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 具有必要的教学培训和实验室经验，成为 独立生物医学研究员。 PI 的近期职业目标是 获得使用超级计算机的知识和实验技能 开发定量分析所必需的电生理学和显微镜学 了解心房兴奋-收缩 (E-C) 耦合。 PL的长期 职业目标是领导一个由生理学家组成的多学科团队， 数学家、医生和计算机程序员在开发 对正常和病理性 E-C 耦合的定量理解 心房细胞。哺乳动物心室细胞具有广泛的横（t）管状结构 快速传导细胞动作电位的系统 从表面到内部触发近乎同步的钙 (Ca) 释放 来自肌浆网 (SR) 和肌原纤维的激活 细胞。心房细胞缺乏广泛的 T 管系统。怎样钙 远离细胞表面的 SR 释放是否被触发尚不清楚。这 总体假设是，在心房细胞中，动作过程中 Ca 进入 电位触发细胞表面 SR 的再生 Ca 释放， 这种再生 Ca 释放（“Ca 波”）以波的形式径向传播到 细胞的中心。具体目标是： (1) 通过以下方式检验该假设： 将心房单细胞收缩率和幅度与 Ca 相关联 使用视频速率二维共焦计算波的速度和幅度 显微镜和荧光 Ca 指示剂。 (2) 建立数学模型 心房细胞 Ca 控制系统并使用数值求解模型 超级计算机。 (3) 通过比较模型的预测来评估模型 通过实验测量电压钳制心房细胞中的 Ca 波 使用共焦显微镜。心房 Ca 控制的定量模型 系统对于理解正常的电-电耦合和起源是必要的 病理性自发 Ca 波，最近的数据表明可以触发 房性心律失常。