Ruthenium Red inhibits the activation of pyruvate dehydrogenase caused by positive inotropic agents in the perfused rat heart

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Abstract
The increases in the amount of active, nonphosphorylated, pyruvate dehydrogenase caused by positive inotropic agents (from a control value of .apprx. 10% to 40% of total enzyme) in the perfused rat heart could be completely blocked by prior perfusion with 2.5 .mu.g of ruthenium red/ml. A similar increase caused by 5 mM-pyruvate was not blocked. This concentration of ruthenium red caused a 25% decrease in contractile force of hearts perfused in the absence of positive inotropic agents; in their presence the contractile force reached teh same value in the absence or presence of ruthenium red. Neither control nor stimulated phosphorylase a content was affected by ruthenium red. Verapamil (0.1 .mu.M) also decreased control contraction (by 40%), but did not block the activation of pyruvate dehydrogenase caused by a rise in extracellular [Ca2+]. Positive inotropic agents apparently activate pyruvate dehydrogenase in rat heart by increasing intramitochondrial [Ca2+].

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