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Oxygen free radicals and calcium homeostasis in the heart
M Kaneko1, Y Matsumoto, H Hayashi
1Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Insights
Oxygen free radicals cause calcium overload in heart cells by disrupting calcium handling. This occurs despite unknown exact radical levels, affecting ATP-independent binding and calcium pumps.
Area of Science:
- Cardiology
- Biochemistry
- Cellular Physiology
Background:
- Oxygen free radicals (OFRs) impact cardiac calcium (Ca2+) homeostasis.
- The precise levels of OFRs in cardiac tissue under physiological and pathophysiological conditions remain largely unknown.
- OFRs are known to induce Ca2+ overload in the heart.
Purpose of the Study:
- To investigate the effects of OFRs on Ca2+ homeostasis in cardiac myocytes.
- To elucidate the mechanisms by which OFRs lead to Ca2+ overload.
- To explore the role of the Na+-Ca2+ exchanger in OFR-induced Ca2+ dysregulation.
Main Methods:
- Review of existing experimental data on OFR effects on cardiac Ca2+ handling.
- Analysis of Ca2+ influx pathways, including Ca2+ channels and the Na+-Ca2+ exchanger.
- Examination of the impact of OFRs on ATP-independent Ca2+ binding, Na+-K+ ATPase, Na+-H+ exchange, and sarcolemmal Ca2+-pump ATPase activity.
Main Results:
- OFRs increase ATP-independent Ca2+ binding but do not increase Ca2+ influx through Ca2+ channels.
- The role of the Na+-Ca2+ exchanger in Ca2+ influx under oxidative stress is unclear, with conflicting effects on Na+-H+ exchange.
- OFRs inhibit sarcolemmal Ca2+-pump ATPase activity, reducing Ca2+ extrusion, and promote Ca2+ release while inhibiting sequestration by the sarcoplasmic reticulum.
Conclusions:
- OFRs induce cardiac Ca2+ overload through multiple mechanisms affecting Ca2+ handling.
- Disruption of Ca2+ extrusion via the sarcolemmal Ca2+-pump ATPase contributes significantly to Ca2+ overload.
- Further research is needed to clarify the precise role and direction of the Na+-Ca2+ exchanger under oxidative stress in the heart.
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 Ca(2+)-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.