Stimulatory Effect of Low Concentrations of Eu3+ on Spontaneous Cardiac Contractions

Abstract

Negative cumulative effects of lanthanides on the human body are well known; they are mainly related to the toxic effects of rare earth metals (REE) on muscle tissue. However, the effects of low concentrations of these metals on muscle are much less well studied. In our work, we identified an unusual stimulatory effect of low concentrations of europium (Eu³⁺) on spontaneous contractions of frog cardiac muscle atrial preparations. The aim of the present study was to investigate the stimulatory effect of europium (Eu³⁺) on the contraction of heart muscle atrial preparations, both normally and in the presence of the mitochondrial respiration inhibitor sodium azide (NaN₃). The study was carried out using two experimental models: muscle preparations obtained from isolated atria of the frog Rana ridibunda heart and mitochondria isolated from the heart of male Wistar rats. As a result of these studies, it was found that Eu³⁺ at a concentration of 0.2 mM, at a temperature of 20°C, potentiated frog atrial contractions in situ, with an increase in both the amplitude and the maximum rate of increase in the strength of single spontaneous contractions. Spontaneous atrial contractions became more resistant to the effects of 1 mM NaN₃. At the same time, Eu³⁺ did not affect the respiration of energized mitochondria, (activated by ADP (state 3) or 2,4-dinitrophenol (state 3U_DNP)). The intensity of this respiration decreased under conditions of calcium loading of mitochondria regardless of the presence of Eu³⁺ in the medium. Thus, on the basis of these studies, it was concluded that Eu³⁺ ions at low concentration (0.2 mM) stimulate atrial contraction and have a positive inotropic effect. The stimulating effect of low concentration of Eu³⁺ on the heart can be explained by synergism in the action of Ca²⁺ and Eu³⁺ on calcium channels, stimulation of Ca²⁺-dependent processes in cardiomyocytes and absence of negative effect on mitochondrial respiration.