© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
[Na+]i handling in the failing human heart
aAbt. Kardiologie und Pneumologie, Zentrum Innere Medizin, Klinik der Georg-August-Universität, Robert-Koch Strasse 40, 37075 Göttingen, Germany
bCardiovascular Research Group, Temple University, Philadelphia, PA, USA
* Corresponding author. Tel.: +49-551-398-925; fax: +49-551-391-9127. pieske{at}med.uni-goettingen.de
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.
KEYWORDS Calcium (cellular); Contractile function; Heart failure; Myocytes; Na/Ca-exchanger
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