AUTHOR=Despa Sanda 

TITLE=Myocyte [Na+]i Dysregulation in Heart Failure and Diabetic Cardiomyopathy

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01303

DOI=10.3389/fphys.2018.01303

ISSN=1664-042X

ABSTRACT=<p>By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na<sup>+</sup> concentration ([Na<sup>+</sup>]<sub>i</sub>) regulates Ca<sup>2+</sup> cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na<sup>+</sup> homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na<sup>+</sup>]<sub>i</sub> is set by the balance between the passive Na<sup>+</sup> entry through numerous pathways and the pumping of Na<sup>+</sup> out of the cell by the Na<sup>+</sup>/K<sup>+</sup>-ATPase. This equilibrium is perturbed in heart failure, resulting in higher [Na<sup>+</sup>]<sub>i</sub>. More recent studies have revealed that [Na<sup>+</sup>]<sub>i</sub> is also increased in myocytes from diabetic hearts. Elevated [Na<sup>+</sup>]<sub>i</sub> causes oxidative stress and augments the sarcoplasmic reticulum Ca<sup>2+</sup> leak, thus amplifying the risk for arrhythmias and promoting heart dysfunction. This mini-review compares and contrasts the alterations in Na<sup>+</sup> extrusion and/or Na<sup>+</sup> uptake that underlie the [Na<sup>+</sup>]<sub>i</sub> increase in heart failure and diabetes, with a particular emphasis on the emerging role of Na<sup>+</sup> - glucose cotransporters in the diabetic heart.</p>