Microdomain modulation of ryanodine receptors in post-myocardial infarction remodeling of cardiac myocytes.
After a myocardial infarction the burden on the surviving heart tissue increases. In response, the cells grow bigger and adapt to maintain the pump function of the heart. Unfortunately, these adaptive changes are limited and the heart now has a reduced work capacity. The changes also carry unwanted consequences as the heart becomes more vulnerable to rhythm disorders. In the current project we examine the changes in one of the key proteins that regulate the calcium homeostasis in the heart muscle cells, the ryanodine receptor. We zoom in on the microdomain around this receptor within the cell to unravel different modulations after myocardial infarction that may relate to oxidative stress. We use advanced imaging modalities to dissect the different microdomains within single cells; we examine the impact of the microdomain changes on the overall cell function for contraction and vulnerability to rhythm disorders. The results will provide novel insights into the molecular workings of the heart and may thereby contribute to the development of targeted therapies for ischemic heart diseases.