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(Circulation Research. 2000;87:641.)
© 2000 American Heart Association, Inc.

Editorial

Increased Na⁺-Ca²⁺ Exchanger in the Failing Heart

Steven M. Pogwizd

From the Department of Medicine, Section of Cardiology, University of Illinois at Chicago.

Correspondence to Steven M. Pogwizd, MD, Department of Medicine, Section of Cardiology, University of Illinois at Chicago, 840 S Wood St, M/C787, Chicago, IL 60612-7323. E-mail spogwizd@uic.edu

Key Words: heart failure • excitation-contraction coupling • Na⁺-Ca²⁺ exchange

	Introduction

 
Heart failure (HF) is a significant problem, affecting more than 2 million people in the United States alone.¹ When severe, it is associated with a 50% 2-year mortality rate attributable to either contractile dysfunction or sudden death from ventricular tachycardia and ventricular fibrillation.¹ The underlying molecular mechanisms have not yet been defined, but there is considerable evidence from studies in experimental models of HF and in the failing human heart that alterations in intracellular Ca²⁺ handling could play a role in both the contractile abnormalities and arrhythmogenicity.^{2 3}

Specifically, HF cardiac myocytes exhibit Ca²⁺ transients with decreased amplitude and prolonged Ca²⁺ decline.^{4 5} These changes have been associated with altered expression and function of several Ca²⁺ regulatory proteins. There has been considerable interest in alterations of sarcoplasmic reticulum (SR) function, particularly the SR Ca²⁺-ATPase (SERCA) and its inhibition by phospholamban. Reduced SERCA mRNA has been noted in animal models of HF^{6 7} and in the failing human heart,^{6 8 9} but alterations in SERCA protein levels and SR Ca²⁺ uptake have been inconsistent and more controversial.^{10 11} The same is true for changes in phospholamban.^{9 10 11 12}

More recently, additional attention has been focused on the Na⁺-Ca²⁺ exchanger (NCX). NCX is a transsarcolemmal protein that plays an important role in controlling levels of [Ca²⁺]_i.¹³ NCX can operate in both a forward mode (Ca²⁺ out, Na⁺ in) and a reverse mode (Na⁺ out, Ca²⁺ in), and most evidence to date¹⁴ has suggested that it does so with a stoichiometry of 3:1 (ie, it exchanges 3 . . . [Full Text of this Article]

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