Na⁺ transport in the normal and failing heart - Remember the balance

In the heart, intracellular Na⁺ concentration ([Na⁺]_i) is a key modulator of Ca²⁺ cycling, contractility and cardiac myocyte metabolism. Several Na⁺ transporters are electrogenic, thus they both contribute to shaping the cardiac action potential and at the same time are affected by it. [Na⁺]_i is controlled by the balance between Na⁺ influx through various pathways, including the Na⁺/Ca²⁺ exchanger and Na⁺ channels, and Na⁺ extrusion via the Na⁺/K⁺-ATPase. [Na⁺]_i is elevated in HF due to a combination of increased entry through Na⁺ channels and/or Na⁺/H⁺ exchanger and reduced activity of the Na⁺/K⁺-ATPase. Here we review the major Na⁺ transport pathways in cardiac myocytes and how they participate in regulating [Na⁺]_i in normal and failing hearts. This article is part of a Special Issue entitled "Na⁺ Regulation in Cardiac Myocytes.".