CORE--ISOLATED MYOCYTE AND WHOLE HEART PHYSIOLOGY

这个核心的两个总体目标之一是为SCOR的项目负责人提供分离心肌细胞和确定分离心肌细胞的收缩功能和钙稳态的设施、专业知识和技术支持。这些实验将主要在转基因小鼠的心脏细胞上进行，并与野生型对照进行比较，尽管也将使用大鼠心脏细胞。一些心脏细胞制剂将用于随后的生化分析(例如，酶分析、Norther和Western blotts)，这些分析将由各个SCOR项目的调查人员执行。第二个主要的超声心动图，并在后来的几年里，从不同的小鼠品系中测量了小鼠的体内血流动力学参数。因此，CORE B将支持SCOR项目负责人在单细胞水平和整个动物环境中评估他们各自的小鼠模型的表型。1.从乳鼠、成年小鼠和大鼠的心房室组织中分离和启动心肌细胞的原代培养。2.测定野生型和转基因小鼠心肌细胞的收缩功能和细胞内钙离子浓度。3.对野生型和转基因小鼠进行M型、二维和多普勒超声心动图研究。4.测量野生型和转基因小鼠的血流动力学参数(如血压、主动脉流量、心输出量、压力-容积环)。5.提供扩张型心肌病研究家系和先证者的临床无创性心功能评估。

One of the two overall objectives of this Core is to provide project leaders in the SCOR with facilities, expertise and technical support for isolating heart cells and determining contractile function and calcium homeostasis in isolated cardiomyocytes. These experiments will be done mainly on heart cells from genetically engineered mice and compared to wild type controls, although rat heart cells will also be used. Some heart cell preparations will be provide for subsequent biochemical analyses (such as, for example, enzyme assays, Norther and Western blots) which will be performed by investigators of the respective SCOR projects. The second main echocardiography and, in later years, measuring in vivo hemodynamic parameters in mice from the various mouse lines. Core B will therefore support SCOR project leaders in assessing the phenotype of their respective mouse models, both on a single cell level as well as in the whole animal context. The Specific Aims are: 1. Isolate and initiate primary cultures of cardiac myocytes from atrial and ventricular tissue of neonatal and adult mice and rats. 2. Measure contractile function and intracellular [Ca2+]i in isolated cardiomyocytes from wild type and genetically engineered mice. 3. Perform M-mode, two dimensional and Doppler echocardiography studies in wild type and genetically engineered mice. 4. Measure hemodynamic parameters (such as blood pressure, aortic flow, cardiac output, pressure volume loops) in wild type and genetically engineered mice. 5. Provide clinical non-invasive evaluation of cardiac function in study families and probands with dilated cardiomyopathy.