Calcium and sodium control in hypoxic-reoxygenated cardiomyocytes.
When oxygen-deprived cardiomyocytes become energy depleted, they accumulate Na+ and Ca2+ in the cytosol. Influx of Ca2+ via the Na+/Ca2+ exchange mechanism seems to contribute to the development of Ca2+ overload, but Ca2+ overload may eventually also occur when this route is blocked. Hypoxic-reoxygenated cardiomyocytes in a state of severe overload of Na+ and Ca2+ can rapidly re-establish a normal cation control when oxidative energy production is re-initiated. The recovery of cellular Ca2+ control may be divided into three stages: first, sequestration of large amounts of Ca2+ into the sarcoplasmic reticulum; second, oscillatory movement of Ca2+ from and back into the sarcoplasmic reticulum and gradual extrusion across the sarcolemma; third, re-establishment of constant low cytosolic Ca2+ concentrations. When the Na+/Ca2+ exchanger is inhibited, extrusion of Ca2+ from the cells' interior is impaired and oscillatory Ca2+ movements between cytosol and sarcoplasmic reticulum continue for long time. Thus, the functions of the sarcoplasmic reticulum and the Na+/Ca2+ exchanger are of crucial importance for the recovery of Ca2+ control in reoxygenated cardiomyocytes. In re-energized cardiomyocytes, a persistent elevation of the cytosolic Ca2+ concentration provokes maximal force development and consecutive mechanical cell injury ("oxygen paradox"). This injury can be prevented when the contractile machinery is inhibited during the initial phase of reoxygenation as long as necessary for the re-establishment of a normal cytosolic Ca2+ control.
Piper
H M
HM
Physiologisches Institut I, Heinrich-Heine-Universität Düsseldorf, FRG.
Siegmund
B
B
Ladilov YuV
Schlüter
K D
KD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D006706:Homeostasis; D000860:Hypoxia / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism* / Q000502:physiology
D012964:Sodium; D010100:Oxygen; D002118:Calcium