The inhibition of calcium uptake and release by rat liver mitochondria by ruthenium red

Abstract

The mucopolysaccharide stain, Ruthenium Red, was shown by Moore [l] to inhibit energy-dependent calcium transport without altering respiration or energy transfer in isolated mitochondria. The studies of Vasington et al. [2] confirmed these observations and further demonstrated that high concentrations of Ruthenium Red inhibit respiration. Currently there seems to be general agreement regarding the inhibitory effect of Ruthenium Red on mitochondrial calcium uptake but some degree of disagreement over the effect(s) of Ruthenium Red on the efflux of calcium from mitochondria. Rossi et al. [3] demonstrated that Ruthenium Red does not promote the release of calcium from mitochondria when added after the calcium uptake is complete. Other laboratories have presented evidence indicating that Ruthenium Red indeed causes the release of calcium from mitochondria pre-loaded with calcium [4,.5]. Also, it has been reported that Ruthenium Red has no effect on uncoupler-induced discharge of calcium from preloaded mitochondria [3,5]. Hence, the previous studies of the effects of Ruthenium Red on mitochondrial calcium metabolism suggest that influx but not efflux of calcium is sensitive to this compound. In the present study it was demonstrated that Ruthenium Red inhibits the release and the re-accumulation of endogenous calcium in rat liver mitochondria. Further, evidence is presented indicating