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Oxygen free radicals and calcium homeostasis in the heart

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Abstract

Many experiments have been done to clarify the effects of oxygen free radicals on Ca2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analayze the results.

It is, however, evident that Ca2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Though ATP-independent Ca2+ binding is increased, Ca2+ influx through Ca2+ channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca2+ can enter the myocytes is Na+−Ca2+ exchanger. Although, the activities of Na+−K+ ATPase and Na+−Ca2+ exchanger. Although, the activities of Na+−H+ exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na+ level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na+−Ca2+ exchange in Ca2+ influx process from extracellular space. Another question is ‘which way does Na+−Ca2+ exchange work under oxidative stress? Net influx or efflux of Ca2+?’ Membrane permeability for Ca2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca2+-pump ATPase activity is depressed by oxygen free radicals, Ca2+ extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca2+ release from sarcoplasmic reticulum and inhibit Ca2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca2+ handling systems could cause the Ca2+ overload due to oxygen free radicals.

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Kaneko, M., Matsumoto, Y., Hayashi, H. et al. Oxygen free radicals and calcium homeostasis in the heart. Mol Cell Biochem 135, 99–108 (1994). https://doi.org/10.1007/BF00925965

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