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(Circulation Research. 2004;95:225.)
© 2004 American Heart Association, Inc.

Editorials

Is Modulation of Sodium-Calcium Exchange a Therapeutic Option in Heart Failure?

Gerd Hasenfuss, Wolfgang Schillinger

From the Georg-August Universität Göttingen, Herzzentrum, Kardiologie und Pneumologie, Göttingen, Germany.

Correspondence to Gerd Hasenfuss, MD, Georg-August-Universität Göttingen, Herzzentrum, Kardiologie und Pneumologie, Robert-Koch-Str. 40, 37099 Göttingen, Germany. E-mail hasenfus@med.uni-goettingen.de

Key Words: Na⁺-Ca²⁺ exchange • calcium • XIP • heart failure • SR function

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Besides the sarcoplasmic reticulum (SR) Ca²⁺-ATPase (SERCA), the sarcolemmal Na⁺-Ca²⁺ exchanger (NCX) is the most important Ca²⁺ transport protein responsible for maintaining the Ca²⁺ balance of the myocyte. It catalyzes the transport of Ca²⁺ across the membrane in exchange for Na⁺ in a reversible manner. Its activity is called "forward" when Na⁺ is transported inward and Ca²⁺ outward and "reversed" when ions are transported in the opposite directions. The driving force of NCX depends on Na⁺ and Ca²⁺ concentrations at either side of the plasma membrane and on the membrane potential. NCX is electrogenic and carries inward (depolarizing) current in forward mode and outward (repolarizing) current in reversed mode.¹ NCX consists of 9 transmembrane helices and a large cytoplasmic loop. This loop has been shown to contain Ca²⁺- and Na⁺-binding regulatory sites, which are distinct from the transport sites. Thus, Na⁺ and Ca²⁺ ions are both transport substrates and modulators of activity. At the N-terminal end of the cytoplasmic loop near the membrane-lipid interface, there is a 20-amino acid segment, designated the endogenous XIP region. This region is considered to function as an autoinhibitory domain that plays a central role in NCX regulation. In addition, PIP₂, protons, ATP, and PKC-dependent effects regulate NCX activity.^1–3 More recently, it was shown that the Ca²⁺ binding protein sorcin exerts stimulatory actions on NCX.⁴

Altered expression and activity of the sarcolemmal NCX may play a key role for disturbed contractile function and arrhythmogenesis in hypertrophy and heart failure. It . . . [Full Text of this Article]

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