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(Circulation Research. 1999;85:982.)
© 1999 American Heart Association, Inc.

Editorials

Sodium-Calcium Exchange

The Phantom Menace

Joshua I. Goldhaber

From the Department of Medicine (Cardiology) and the Cardiovascular Research Laboratories, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Joshua I. Goldhaber, MD, UCLA School of Medicine, Division of Cardiology, 47-123 CHS, 10833 LeConte Ave, Los Angeles, CA 90095-1679. E-mail jgoldhaber@mednet.ucla.edu

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

	Introduction

 
Researchers have been aware of the existence of a membrane transporter in cardiac myocytes that exchanged calcium for sodium for more than 30 years.¹ In that period of time, even as the molecular details of the sodium-calcium exchanger (NaCaX) were being worked out, its physiological role had still not been clearly defined. Early reports focused on the role of the exchanger as an important source of Ca²⁺ influx² and as a regulator of contractile force, an important issue given that the most commonly used inotropic agent at the time was digitalis.³ By the mid-1980s, when it had become clear that Ca²⁺ entry via L-type Ca²⁺ channels was the major trigger for contractile Ca²⁺ release from the sarcoplasmic reticulum (SR), it became widely accepted that the chief role of the exchanger was to remove Ca²⁺ from the cytosol during diastole. Interest in the exchanger as an important Ca²⁺ entry mechanism resurfaced early in this decade when LeBlanc and Hume⁴ demonstrated sodium-current–dependent Ca²⁺ influx via the exchanger, capable of triggering contraction; however, this idea has remained controversial. Now, as we approach the new millennium and study excitation-contraction (E-C) coupling at the subcellular level,^{5 6} the importance of the exchanger as a modulator of Ca²⁺ release and E-C coupling gain is becoming clearer.^{7 8}

The pathophysiological roles of the exchanger have been much less controversial. In the ischemic/reperfused heart, a rise in intracellular sodium⁹ frustrates the ability of the exchanger to remove Ca²⁺.¹⁰ Stimulation of the exchanger by oxygen free radicals may further accelerate . . . [Full Text of this Article]

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