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Inhibition of the mitochondrial calcium uniporter by the oxo‐bridged dinuclear ruthenium amine complex (Ru 360 ) prevents from irreversible injury in postischemic rat heart
Author(s) -
de Jesús GarcíaRivas Gerardo,
GuerreroHernández Agustín,
GuerreroSerna Guadalupe,
RodríguezZavala José S.,
Zazueta Cecilia
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04771.x
Subject(s) - ryanodine receptor , uniporter , mitochondrial permeability transition pore , calcium , ruthenium red , mitochondrion , voltage dependent calcium channel , chemistry , biophysics , microbiology and biotechnology , biology , biochemistry , cytosol , programmed cell death , apoptosis , enzyme , organic chemistry
Mitochondrial calcium overload has been implicated in the irreversible damage of reperfused heart. Accordingly, we studied the effect of an oxygen‐bridged dinuclear ruthenium amine complex (Ru 360 ), which is a selective and potent mitochondrial calcium uniporter blocker, on mitochondrial dysfunction and on the matrix free‐calcium concentration in mitochondria isolated from reperfused rat hearts. The perfusion of Ru 360 maintained oxidative phosphorylation and prevented opening of the mitochondrial permeability transition pore in mitochondria isolated from reperfused hearts. We found that Ru 360 perfusion only partially inhibited the mitochondrial calcium uniporter, maintaining the mitochondrial matrix free‐calcium concentration at basal levels, despite high concentrations of cytosolic calcium. Additionally, we observed that perfused Ru 360 neither inhibited Ca 2+ cycling in the sarcoplasmic reticulum nor blocked ryanodine receptors, implying that the inhibition of ryanodine receptors cannot explain the protective effect of Ru 360 in isolated hearts. We conclude that the maintenance of postischemic myocardial function correlates with an incomplete inhibition of the mitochondrial calcium uniporter. Thus, the chemical inhibition by this molecule could be an approach used to prevent heart injury during reperfusion.