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31 October 2012

The Na+/Ca2+ exchanger in cardiac ischemia/reperfusion injury

Sai Chen, Shuzhuang Li

DOI: 10.12659/MSM.883533

Med Sci Monit 2012; 18(11): RA161-165


The Na+/Ca2+ exchanger (NCX) is an important electrogenic transporter in maintaining Na+ and Ca2+ homeostasis in a variety of mammalian organs, and is involved in the physiological and pathophysiological regulation of Ca2+ concentration in the myocardium. It can affect cardial structure, electrophysiology and contractile properties. The role of the NCX in heart cells following ischemia/reperfusion (IR) has been investigated using a number of in vitro and in vivo models. During ischemia, ionic disturbances favor Ca2+-influx mode activity as excess Na+ is extruded in exchange for Ca2+, giving rise to increased intracellular Ca2+ levels (Cai). This rise in Cai contributes to reversible cellular dysfunction upon reperfusion, such as myocardial necrosis, arrhythmia, systolic dysfunction and heart failure. We have reviewed the major in vivo and in vitro cardiac IR-related NCX studies in an attempt to clarify the functions of NCX in IR and conclude that recent studies suggest blockage of NCX has potential therapeutic applications. Although the use of different IR models, application of NCX stimulators and inhibitors, and development of NCX transgenic animals do help elucidate the role of this ion exchanger in heart cells, related mechanisms are not completely understood and clinically effective specific NCX inhibitors need further research.

Keywords: Myocardial Reperfusion Injury - physiopathology, Myocardial Contraction, Heart Failure - physiopathology, Arrhythmias, Cardiac - physiopathology, Necrosis, Sodium-Calcium Exchanger - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750