Calcium Waves in Atrial Cells

描述（由申请人提供）： 该培训补助金旨在为主要研究者（PI） 具有必要的教学培训和实验室经验， 独立的生物医学研究员私家侦探？的直接职业目标是 掌握使用超级计算机的知识和实验技能， 电生理学和显微镜必要的发展定量 心房兴奋-收缩（E-C）耦合。Pl？的长期 职业目标是领导一个多学科的生理学家团队， 数学家，医生和计算机程序员在开发一个 定量了解正常和病理性E-C耦合， 心房细胞哺乳动物心室细胞有广泛的横（t）管 快速传导细胞动作电位的系统 从表面到内部，触发几乎同步的钙（Ca）释放 从肌浆网（SR）和整个肌原纤维的激活 牢房心房细胞缺乏广泛的t管系统。怎么样 从远离细胞表面的SR的释放被触发尚不清楚。的 总的假设是，在心房细胞中，动作期间的Ca内流 电位触发细胞表面SR的再生Ca释放， 这种再生的Ca释放（“Ca波”）作为波径向传播到 细胞的中心。具体目的是：（1）通过以下方式检验这一假设： 心房单细胞收缩率和幅度与Ca 挥手？s速度和振幅使用视频率二维共焦 显微镜和荧光Ca指示剂。(2)建立一个数学模型 心房细胞Ca ~（2+）控制系统，并利用 超级计算机(3)通过比较模型来评估模型？的预言 电压钳位心房细胞Ca波的实验测量 使用共聚焦显微镜。心房肌钙调控的定量模型 系统对于理解正常的E-C耦合和起源都是必要的 病理性自发钙波，最近的数据表明， 房性心律失常

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.