1 [ Na ] handling in the failing human hearti

Proper contractile function of the heart depends on intact excitation–contraction processes and ion homeostasis of the myocytes. The 21 21 1 Ca ion activates contraction through its binding to troponin C. However, Ca homeostasis is tightly linked to Na regulation because 21 1 21 21 the primary mechanism for Ca efflux in cardiac myocytes is via electrogenic Na /Ca -exchange. While altered Ca -homeostasis has 1 been demonstrated in animal models of heart failure and failing human cardiac tissue, the role of dysfunctional Na handling processes in 1 altered excitation–contraction coupling remains obscure. Furthermore, altered Na handling has been implicated in a wide range of 1 cellular processes, such as regulation of membrane potential, pH, and growth. This review will discuss (1) the evidence for altered [Na ]i 1 21 homeostasis in the failing human heart, (2) how alterations in the Na electrochemical gradient can influence Ca handling, contractile 1 function, and a number of other cellular processes, and (3) the potential defects in Na channels and transporters that may underlie altered 1 [Na ] in the failing human heart. i  2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.