Heart failure (HF) is the highest contributor to mortality in the United States. HF is associated with certain cellular aspects like electrolyte and ionic imbalances.  Studies have shown that lower levels of serum chloride concentration were elicited in patients with chronic heart failure. However, little is known about the role of chloride in cardiac physiology. Therefore, our goal is to characterize the role of chloride in cardiac contractility and function. Using chloride sensors and whole-cell patch clamping, we will study the role of chloride ion in primary cardiomyocytes. To further understand the mechanism of chloride homeostasis in the cell, we will explore the chloride intracellular ion channel (CLIC) in cardiomyocytes. Previous studies in our lab have exhibited that CLIC5 and CLIC4 are localized in cardiac mitochondria. Specific changes in extracellular Cl- concentration might correlate to CLICs present on the mitochondria, thus affecting the mitochondria functioning. Reaction Oxygen Species (ROS) production is higher in CLIC5 knockout mice. Therefore, we will study the metabolic and electrophysiological changes in cardiomyocyte mitochondria in varying Cl- concentrations. This study will help clarify the role of chloride in cardiac function and develop better drug targets for chronic HF.

Publications:
Shubha Gururaja Rao, Devasena Ponnalagu, Sowmya Sukur, Harkewal Singh, Shridhar Sanghvi, Yixiao Mei, Ding J. Jin & Harpreet Singh. Identification and Characterization of a Bacterial Homolog of Chloride Intracellular Channel (CLIC) Protein. Sci. Rep., 2017,7,8500.