Grant: China-Canada Joint Health Research Initiative

After heart attacks and in heart failure, changes occur to the heart in its ability to pump blood and underlying this are often changes in the structure of the heart and in the functioning of the cells that compose it. We call these changes in the heart's structure and electrical activity "remodeling." Understanding remodeling is central to predicting the progress and severity of the disease. The aim of this project is to understand how proteins that regulate the electrical activity of the heart are processed by the cells that make up the heart and how those proteins are transported to and from their place of function and sent to be broken down when they are worn out. Very little is known about how these processes occur in heart cells and how it works for proteins called potassium ion channels that are very important in the normal electrical activity of these cells and, thus, the heart. This project aims to learn what "trucks" and "containers" are used to transport these potassium ion channels around the cell and how the cell decides whether to reuse or take apart a potassium ion channel that it has temporarily or permanently removed from its place of function. We have developed new systems that allow, for the first time, the ready introduction of outside genes into muscle cells isolated from real heart. We will use these systems to introduce proteins (defective "trucks," "truck parts," "containers," etc.) to interfere with normal trafficking. We will thereby determine for the first time how the movement of potassium ion channels is carried out in heart cells, and how that movement is changed when a heart becomes diseased. Ultimately, this work may lead to new ways to intervene and perhaps prevent the progression of heart diseases and, perhaps, allow interventions to correct some of the underlying defects that lead to heart disease in the first place.