CALCIUM AND SODIUM CONTROL IN HYPOXIC-REOXYGENATED CARDIOMYOCYTES

When oxygen-deprived cardiomyocytes become energy depleted, they accum ulate Na+ and Ca2+ in the cytosol. Influx of Ca2+ via the Na+/Ca2+ exc hange mechanism seems to contribute to the development of Ca2+ overloa d, but Ca2+ overload may eventually also occur when this route is bloc ked. 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 devided into three stages: first, sequestration o f large amounts of Ca2+ into the sarcoplasmic reticulum; second, oscil latory movement of Ca2+ from and back into the sarcoplasmic reticulum and gradual extrusion across the sarcolemma; third, re-establishment o f constant low cytosolic Ca2+ concentrations. When the Na+/Ca2+ exchan ger is inhibited, extrusion of Ca2+ from the cells' interior is impair ed and oscillatory Ca2+ movements between cytosol and sarcoplasmic ret iculum continue for long time. Thus, the functions of the sarcoplasmic reticulum and the Na+/Ca2+ exchanger are of crucial importance for th e recovery of Ca2+ control in reoxygenated cardiomyocytes. In re-energ ized cardiomyocytes, a persistent elevation of the cytosolic Ca2+ conc entration provokes maximal force development and consecutive mechanica l cell injury (''oxygen paradox''). This injury can be prevented when the contractile machinery is inhibited during the initial phase of reo xygenation as long as necessary for the re-establishment of a normal c ytosolic Ca2+ control.