RECONSTRUCTION AND MODELING OF NORMAL AND GENETICALLY ENGINEERED MOUSE HEART

正常和基因工程小鼠心脏的重建和建模

• 批准号: 7722378
• 负责人: RICHARD VAUGHAN-JONES
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722378
• 关键词: Acidosis; Acids; Architecture; Cardiac; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Genetically Engineered Mouse; Grant; Heart; Heterogeneity; Institution; Modeling; Protons; Research; Research Personnel; Resources; Series; Source; United States National Institutes of Health; Ventricular; base; novel; pH gradient; protein distribution; reconstruction; three-dimensional modeling

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to investigate the arrhythmogenic consequences of regional acidosis within the cardiac ultrastructure by developing a hierarchical series of novel integrative 3D models which will incorporate increasingly more complex details of the subcellular architecture, spatial heterogeneities of protein distribution, and interacting effects of protons on normal Ca2+ and Na+ transport and ECC. These models will be used to predict 1) pH gradients resulting from heterogeneity of acid-base transporters around a single t-tubule, 2) potential interactions of pH gradients on normal Ca2+ and Na+ transport around a single t-tubule and 3) consequences of the pH gradients on normal ECC in an anatomically accurate cross-section of a ventricular cell.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们建议通过开发一系列分层的新型综合 3D 模型来研究心脏超微结构内局部酸中毒的致心律失常后果，该模型将纳入亚细胞结构、蛋白质分布的空间异质性以及质子对正常 Ca2+ 的相互作用的日益复杂的细节。以及Na+运输和ECC。这些模型将用于预测 1) 由单个 t 管周围酸碱转运蛋白的异质性引起的 pH 梯度，2) pH 梯度对单个 t 管周围正常 Ca2+ 和 Na+ 转运的潜在相互作用，以及 3)心室细胞解剖学上精确的横截面中正常 ECC 的 pH 梯度。