[Does altered regulation of Na+ cause reduced myocardial contractility in heart failure?]

Cardiac contractility is largely regulated through transients in intracellular Ca2+ concentration [Ca2+]i. [Ca2+]i is under the influence of the sarcolemmal Na+/Ca2+ exchanger that exchanges Ca2+ for Na+ and which is mainly regulated by the intracellular Na+ concentration ([Na+]i). Consequently, [Na+]i influences cardiac contractility. [Na+]i is regulated by numerous proteins: Na+/K+ adenosine triphosphatases (ATPases), Na+-channels and Na+/H+ exchangers that control and are controlled by [Na+]i. In particular, the Na+/K+ ATPase and its crosstalk with the other proteins controls the intracellular level of Na+.

This review focuses on the significance of an efficient crosstalk between the topical proteins for control of [Na+]i.

Co-localised proteins will sense the same [Na+]i; this is important as [Na+]i seems to vary in different parts of the cell. Evidence suggests that the regulation of [Na+]i is altered in heart failure. Several transport proteins have altered activity and expression patterns and this could partially explain the reduced contractility in heart failure.

A better understanding of the control of [Na+]i may lead to a new therapy for heart failure.