CORE--ISOLATED MYOCYTE AND WHOLE HEART PHYSIOLOGY

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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.