Grant: Discovery Grants Program - Individual

Calcium ion cycling determines heart function and heart muscle cell survival/death. The calcium cycling is regulated by calcium release unit of sarcoplasmic reticulum. This unit keeps calcium cycling properly, a process important for heart contract and relaxation. However, the nature of calcium release unit homeostasis has not been fully understood in heart muscle cells. This program of research is proposed to investigate how a structural protein called "junctophilin-2" maintains the normality of calcium release unit in heart muscle cells. Specifically, we will examine how junctophilin-2 protects another protein called "junctin" in heart muscle cells as junctin is an important component of the calcium release unit. Without junctin, the calcium release unit does not work properly and increases calcium ion release from sarcoplasmic reticulum, leading to perturbation of calcium homeostasis in heart muscle cells. Dysregulation of calcium cycling not only directly damages heart function but also causes heart muscle cell death. Thus, we will also examine whether protection of junctin is a mechanism by which junctophilin-2 keeps calcium release unit working properly. This program of research will provide molecular basis for junctophilin-2 regulation of junctin in the calcium release unit and its influence on calcium cycling. Thus, the outcomes of our research program will significantly increase our understanding of the nature of calcium cycling in heart muscle cells, a fundamental mechanism for maintaining heart working properly, which will bridge the knowledge gap in the field of heart biology and physiology which will benefit the research community of heart biology and physiology. Furthermore, since heart is one of the most important organs our research program will also pave the way toward further studying the mechanisms and treatments for heart diseases, which will eventually benefit patients with heart diseases in Canada and other countries in the world.