SR CA ATPASE, A DETERMINANT OF CARDIAC CONTRACTILITY

描述(改编自申请者的描述)：中心假设 肌浆网钙-ATPase(SERCA)是一种 心肌收缩能力的关键决定因素。该提案有四个方面 具体问题(目标)。具体目标1：是否存在动态平衡机制 在心肌细胞内能够感觉到 SERCA水平和发展补偿机制？具体目标2：什么是 肌浆网钙摄取增加或减少对心脏功能的影响 心肌细胞内的整体钙稳态？具体目标3：什么 肌浆网钙转运改变对心肌的功能影响 性能。具体目标4：SERCA在心肌肥厚中的作用 还有心力衰竭？这些问题将在转基因小鼠身上进行研究。 SERCA(SERCA2a和SERCA1a)在转基因小鼠中的过表达 SERCA(SERCA基因敲除小鼠(+/-))减少。

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 (+/-)).