Calcium and sodium control in hypoxic-reoxygenated cardiomyocytes.

When oxygen-deprived cardiomyocytes become energy depleted, they accumulate Na and Ca in the cytosol. Influx of Ca via the Na/Ca exchange mechanism seems to contribute to the development of Ca overload, but Ca overload may eventually also occur when this route is blocked. Hypoxic-reoxygenated cardiomyocytes in a state of severe overload of Na and Ca can rapidly re-establish a normal cation control when oxidative energy production is re-initiated. The recovery of cellular Ca control may be devided into three stages: first, sequestration of large amounts of Ca into the sarcoplasmic reticulum; second, oscillatory movement of Ca from and back into the sarcoplasmic reticulum and gradual extrusion across the sarcolemma; third, re-establishment of constant low cytosolic Ca concentrations. When the Na/Ca exchanger is inhibited, extrusion of Ca from the cells' interior is impaired and oscillatory Ca movements between cytosol and sarcoplasmic reticulum continue for long time. Thus, the functions of the sarcoplasmic reticulum and the Na/Ca exchanger are of crucial importance for the recovery of Ca control in reoxygenated cardiomyocytes. In re-energized cardiomyocytes, a persistent elevation of the cytosolic Ca 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 Ca control. [ABSTRACT FROM AUTHOR]