Effect of Suramin on Mitochondrial Membrane Potential
DOI:
https://doi.org/10.29038/2617-4723-2018-377-100-107Keywords:
RyRs, mRyRs, suramin, Δψ, substrates for oxidationAbstract
It is known that suramin is an agonist of the ryanodine sensitive Ca2+-channels of the endoplasmic reticulum (RyRs). We hypothesized that it may be an agonist of mitochondrial ryanodine sensitive Ca2+-channels (mRyRs) too. The effect of suramin on mitochondrial membrane potential of hepatocytes was investigated for the test of the hypothesis. Suramin (1 μM) and isolated mitochondria were added one after another and then membrane potential was recorded. Measurement of the membrane potential of mitochondria was carried out using methyltriphenylphosphonium (ТРМР+) sensitive electrode. Succinate (5 mM), pyruvate (5 mM) or α-ketoglutarate(5 mM) and ADP (320 nM) were added, respectively, to initiate respiration and to stimulate oxidative phosphorylation. It has been established that the effect of suramin on the mitochondrial membrane potential depends on the presence substrates for oxidation and phosphorylation in the medium of incubation. Under the influence of suramin, the membrane potential of mitochondria during oxidation of exogenous succinate in the state of S4 by Chance and Williams (1955) decreased for 5.88% relative to control. This is possibly caused by the usage of energy of the membrane potential of mitochondria for the transport of Ca2+ ions to the mitochondrial matrix. The suramine increased the mitochondrial membrane potential in the state S4 for 15.2% during oxidation of α-ketoglutarate, and with oxidation of pyruvate - for 39.1% relative to control. These increases in the mitochondrial membrane potential are possibly associated with activation of α-ketoglutarate dehydrogenase or pyruvate dehydrogenase complexes, which, in contrast to succinate dehydrogenase, are Ca2+ -dependent enzymes. Consequently, suramin at a concentration of 1 μM, activates mitochondrial ryanodine sensitive Ca2+-channels of rat hepatocytes and causes an increase in Ca2+ intake to mitochondrial matrix by activation of Ca2+-dependent dehydrogenases, and an increase in the membrane potential of mitochondria.
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