Myocyte [Na] Dysregulation in Heart Failure and Diabetic Cardiomyopathy.

By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na concentration ([Na]) regulates Ca cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na] is set by the balance between the passive Na entry through numerous pathways and the pumping of Na out of the cell by the Na/K-ATPase. This equilibrium is perturbed in heart failure, resulting in higher [Na]. More recent studies have revealed that [Na] is also increased in myocytes from diabetic hearts. Elevated [Na] causes oxidative stress and augments the sarcoplasmic reticulum Ca leak, thus amplifying the risk for arrhythmias and promoting heart dysfunction. This mini-review compares and contrasts the alterations in Na extrusion and/or Na uptake that underlie the [Na] increase in heart failure and diabetes, with a particular emphasis on the emerging role of Na - glucose cotransporters in the diabetic heart.