Using human induced pluripotent stem cell derived cardiomyocytes as a model for catecholaminergic polymorphic ventricular tachycardia: Visualizing calcium handling

Cardiovascular diseases are one of the leading causes of death in the developed world. Human induced pluripotent stem cell derived cardiomyocytes are a relatively novel model for studying cardiovascular diseases that have the advantage of being of human origin over conventional animal models. Calcium handling is an important aspect in causing diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), therefore monitoring Ca2+ kinetics within the cardiomyocytes is an important aspect for studying those diseases. This project proposes the design and use of a genetically encoded calcium indicator, R-CEPIA1SR, in combination with traditional calcium sensitive dyes in order to monitor both the cytosolic and sarcoplasmic reticulum luminal calcium levels simultaneously. The optogenetic constructs BLINK2 and Phobos can further help control the cell for easier observation of Ca2+ events. This will lead to a better understanding of the mechanisms behind CPVT related variants and eventually lead to better treatments in combating them.