[Na+]i handling in the failing human heart.
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.
Pieske
Burkert
B
Abt. Kardiologie und Pneumologie, Zentrum Innere Medizin, Klinik der Georg-August-Universität, Robert-Koch Strasse 40, 37075, Göttingen, Germany. pieske@med.uni-goettingen.de <pieske@med.uni-goettingen.de>
Houser
Steven R
SR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D012964:Sodium; D002118:Calcium