Effect of plague murine toxin on the uptake of calcium and inorganic phosphate ions by heart mitochondria

Abstract

Plague murine toxin can inhibit to a significant extent the uptake of Ca ++ and inorganic phosphate (P i) by rat heart mitochondria in the presence of succinate, α-ketoglutarate, malate, or β-hydroxybutyrate as the respiratory substrate. When these mitochondrial suspensions are incubated with ATP, but without a respiratory substrate, the uptake of these ions is also inhibited by the toxin. Although the toxin does not alter rat heart mitochondrial respiration supported by the oxidation of reduced cytochrome c, it does inhibit the uptake of Ca ++ and P i supported by this segment of the electron transport chain. When toxin is inactivated by treatment with formalin, it has little or no effect on the uptake of Ca ++ or P i by rat heart mitochondria in any of the systems investigated. The uptake of these ions by heart mitochondria isolated from the toxin-resistant rabbit is either not inhibited at all by the toxin or is inhibited to a much lesser extent as compared with rat heart mitochondria. Ethylenediaminetetraacetic acid, at a concentration which does not inhibit Ca ++ or P i uptake but does prevent swelling, prevents to a large extent the inhibitory effect of the toxin on the accumulation of these ions by rat heart mitochondria.