Abstract
By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na(+) concentration ([Na(+)](i)) regulates Ca(2+) 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(+)](i) 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(+)](i). More recent studies have revealed that [Na(+)](i) is also increased in myocytes from diabetic hearts. Elevated [Na(+)](i) causes oxidative stress and augments the sarcoplasmic reticulum Ca(2+) 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(+)](i) increase in heart failure and diabetes, with a particular emphasis on the emerging role of Na(+) - glucose cotransporters in the diabetic heart.