Localization and function of SERCA2 in the normal and failing heart
I. The purpose of the project: It is well established that heart failure can result from reduced function of individual cardiac muscle cells (cardiomyocytes). Impaired contraction and relaxation of individual cells can, in turn, result from changes in calcium homeostasis including disrupted release and re-tupake into a compartment called the sarcoplasmic reticulum (SR). The precise reasons for these alterations are unclear, but we believe that they at least partly result from altered activity of an SR calcium pump called SERCA. In our project, we aim to perform a detailed investigation of calcium handling during heart failure, with particular attention given to the precise three dimensional sub-cellular arrangement of SERCA. We will additionally examine the importance of SERCA localization and function for triggering cardiac arrhythmia and weakened whole-heart function during heart failure.
II. The expected adverse effects on the animals: moderate burden (moderat belastende)
III. The expected benefits for society: We anticipate that this work will lead to the discovery of novel drug targets for heart failure patients, which is essential for reducing the socioeconomic burden of this disease.
IV. The number of animals and species: 2224 mice
V. How will the requirements for 3R be accomplished by the project: When possible, cells, tissue and data from these animals will be shared between researchers to reduce animal usage.
II. The expected adverse effects on the animals: moderate burden (moderat belastende)
III. The expected benefits for society: We anticipate that this work will lead to the discovery of novel drug targets for heart failure patients, which is essential for reducing the socioeconomic burden of this disease.
IV. The number of animals and species: 2224 mice
V. How will the requirements for 3R be accomplished by the project: When possible, cells, tissue and data from these animals will be shared between researchers to reduce animal usage.