Involvement of Na+/Ca2+ Exchange in Normal Cardiac Excitation-Contraction Coupling and in Ca2+ Overload during Ischemia and Reperfusion

  • Hiroshi Satoh
  • Hideki Katoh
  • Hajime Terada
  • Hideharu Hayashi
Part of the Progress in Experimental Cardiology book series (PREC, volume 6)


The Ca2+ overload is known to play a major role in cellular dysfunction and death in ischemic and reperfused myocardium. The sarcolemmal Na+/Ca2+ exchange (NCX) is one of the essential regulators of Ca2+ homeostasis in normal excitation-contraction (E-C) coupling and can be a possible route for Ca2+ overload during ischemia and reperfusion. NCX is a bidirectional transport process, capable of moving Ca2+ in either direction across the sarcolemma, depending on the membrane potential and the transmembrane gradients of Na+ and Ca2+. In normal E-C coupling, NCX mainly operates to extrude Ca2+ from cytoplasm and the role of Ca2+ entering via NCX seems to be rather small, although there may be species difference. During ischemia, the decrease in Ca2+ efflux via the forward mode of NCX by high [Na+]i,membrane depolarization, low pHi, and low ATP would delay the Ca2+ transient decay and would increase diastolic [Ca2+]i. After reperfusion, the recovery of NCX activity, with sustained cellular Na+ loading, can induce Ca2+ influx via the reverse mode of NCX, causing spontaneous Ca2+ release from the sarcoplasmic reticulum and triggered arrhythmias. While there are some possible therapeutic agents which may reduce ischemia/reperfusion injury, a relatively specific blocker of the reverse mode of NCX has been shown to protect myocardium from Ca2+ overload. These findings indicate the importance of NCX for normal E-C coupling and Ca2+ overload in ischemia/reperfusion injury, and the possibility of specific and clinically useful drugs targeting NCX.


Na+/Ca2+ exchange excitation-contraction coupling ischemia and reperfusion Ca2+ overload 


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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Hiroshi Satoh
    • 1
  • Hideki Katoh
    • 1
  • Hajime Terada
    • 1
  • Hideharu Hayashi
    • 1
  1. 1.Division of Cardiology, Internal Medicine IIIHamamatsu University School of MedicineHamamatsuJapan

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