In vitro and in silico analysis of sodium-dependent regulation of mitochondrial calcium concentration and production of reactive oxygen species in rabbit ventricular myocytes

Abstract

Increased intracellular Na concentration ([Na]i) is a hallmark of cardiomyocyte remodeling in heart failure (HF), a chronic condition characterized by impaired contractility, metabolic imbalance, and arrhythmia susceptibility. Although Na homeostasis is central to cardiomyocyte function, its contribution to the sequelae of disease is still largely unexplored. We previously demonstrated that Na overload plays a critical role in promoting Ca-dependent arrhythmias in failing ventricular myocytes by interacting with the Ca/calmodulin-dependent protein kinase II (CaMKII) signaling.