SR CA ATPASE, A DETERMINANT OF CARDIAC CONTRACTILITY

SR CA ATP酶，心脏收缩力的决定因素

• 批准号: 6343665
• 负责人: Muthu Periasamy
• 金额: $ 14.49万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-15 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343665
• 关键词: RNase protection assay; autoradiography; calcineurin; calcium binding protein; calcium channel; calcium transporting ATPase; cellular pathology; disease /disorder model; electrophysiology; enzyme activity; gene expression; gene targeting; genetically modified animals; heart contraction; heart failure; homeostasis; laboratory mouse; membrane transport proteins; messenger RNA; myocardium; phospholamban; phosphorylation; sarcoplasmic reticulum; ventricular hypertrophy; western blottings

DESCRIPTION (adapted from the applicant's description): The central hypothesis of this proposal is that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) is a critical determinant of myocardial contractility. The proposal has four specific questions (aims). Specific aim 1: Are there homeostatic mechanisms within the cardiac myocyte that are capable of sensing perturbations in the level of SERCA and developing compensatory mechanisms? Specific aim 2: What are the functional consequences of increased or decreased SR calcium uptake on the overall calcium homeostasis within the cardiac myocyte? Specific aim 3: What are the functional consequences of altered SR calcium transport on myocardial performance. Specific aim 4: What is the role of SERCA in cardiac hypertrophy and heart failure? These questions will be studied in transgenic mice with an overexpression of SERCA (both SERCA2a and SERCA1a) and in transgenic mice with a decrease in SERCA (SERCA knockout mice (+/-)).

描述（改编自申请人的描述）：中心假设 肌浆网Ca ~（2+）-ATP酶（SERCA）是一种重要的钙离子转运蛋白。 心肌收缩力的关键决定因素。该提案有四个 具体问题（目标）。具体目标1：是否存在稳态机制 在心肌细胞内，它们能够感知 SERCA水平和发展补偿机制？具体目标2： 增加或减少SR钙摄取对 心肌细胞内的整体钙稳态？具体目标3：什么 是改变SR钙转运对心肌细胞的功能影响， 性能具体目标4：SERCA在心肌肥厚中的作用 和心力衰竭吗这些问题将在转基因小鼠中进行研究， SERCA（SERCA 2a和SERCA 1a）的过表达，并且在具有 SERCA降低（SERCA敲除小鼠（+/-））。