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

Negative cumulative effects of lanthanides on the human bodyare well known; they are mainly related to the toxic effects ofrare earth metals (REE) on muscle tissue. However, the effects oflow concentrations of these metals on muscle are much less wellstudied. In our work, we identified an unusual stimulatory effectof 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 effectof europium (Eu³⁺) on the contractionof heart muscle atrial preparations, both normally and in the presenceof the mitochondrial respiration inhibitor sodium azide (NaN₃).The study was carried out using two experimental models: musclepreparations obtained from isolated atria of the frog Rana ridibunda heart and mitochondriaisolated from the heart of male Wistar rats. As a result of thesestudies, it was found that Eu³⁺ at aconcentration of 0.2 mM, at a temperature of 20°C, potentiated frogatrial contractions in situ, with an increase in both the amplitudeand the maximum rate of increase in the strength of single spontaneouscontractions. Spontaneous atrial contractions became more resistantto the effects of 1 mM NaN₃. At the sametime, Eu³⁺ did not affect the respirationof energized mitochondria, (activated by ADP (state 3) or 2,4-dinitrophenol(state 3U_DNP)). The intensity of this respirationdecreased under conditions of calcium loading of mitochondria regardlessof the presence of Eu³⁺ in the medium.Thus, on the basis of these studies, it was concluded that Eu³⁺ ionsat low concentration (0.2 mM) stimulate atrial contraction and havea positive inotropic effect. The stimulating effect of low concentrationof Eu³⁺ on the heart can be explainedby synergism in the action of Ca²⁺ and Eu³⁺ oncalcium channels, stimulation of Ca²⁺-dependentprocesses in cardiomyocytes and absence of negative effect on mitochondrialrespiration.