Altered intracellular sodium homeostasis in the failing human heart influences calcium handling, contractile function, and other cellular processes through defects in sodium channels and transporters.
This review highlights the critical role of dysfunctional intracellular sodium handling in altered excitation-contraction coupling and cellular processes in heart failure.
Proper contractile function of the heart depends on intact excitation-contraction processes and ion homeostasis of the myocytes. The Ca2+ ion activates contraction through its binding to troponin C. However, Ca2+ homeostasis is tightly linked to Na+ regulation because the primary mechanism for Ca2+ efflux in cardiac myocytes is via electrogenic Na+/Ca2+-exchange. While altered Ca2+-homeostasis has been demonstrated in animal models of heart failure and failing human cardiac tissue, the role of dysfunctional Na+ handling processes in altered excitation-contraction coupling remains obscure. Furthermore, altered Na+ handling has been implicated in a wide range of cellular processes, such as regulation of membrane potential, pH, and growth. This review will discuss (1) the evidence for altered Na+i homeostasis in the failing human heart, (2) how alterations in the Na+ electrochemical gradient can influence Ca2+ handling, contractile function, and a number of other cellular processes, and (3) the potential defects in Na+ channels and transporters that may underlie altered Na+i in the failing human heart.
Burkert Pieske (Sat,) conducted a review in Heart failure. Altered [Na+]i homeostasis was evaluated. Altered intracellular sodium homeostasis in the failing human heart influences calcium handling, contractile function, and other cellular processes through defects in sodium channels and transporters.