Stimulating effect of low concentrations of Eu3+ on spontaneous cardiac contractions

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Abstract

The negative cumulative effects of lanthanides on the human body are well known; they are associated mainly with the toxic effects of rare earth metals (REE) on muscle tissue. However, the effects of low concentrations of these metals on muscle are less understood. In our work, we found out an unusual stimulating effect of low concentrations of europium (Eu3+) on spontaneous contractions of atria of a frog. The purpose of this study was to study the stimulating effect of Eu3+ on the contraction of atria, 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 heart of the frog Rana ridibunda and mitochondria isolated from the heart of male Wistar rats. As a result of the studies, it was established that Eu3+ in a concentration of 0.2 mM, at a temperature of 20°C, potentiated contractions of the frog atria in situ; both the amplitude and the maximum rate of increase of single spontaneous contractions increased. 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 3UDNP). The intensity of this respiration decreased after the calcium load of mitochondria, regardless of the presence of Eu3+ in the medium. Thus, Eu3+ ions at low concentrations (0.2 mM) stimulated atrial contraction and had a positive inotropic effect. The stimulating effect of low concentrations of Eu3+ on the heart can be explained by the synergism in the action of Ca2+ and Eu3+ on calcium channels, stimulation of Ca2+-dependent processes in cardiomyocytes and the absence of a negative effect on mitochondrial respiration.

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About the authors

K. V. Sobol

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences

Author for correspondence.
Email: peep9@yandex.ru
Russian Federation, St. Petersburg

S. M. Korotkov

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences

Email: peep9@yandex.ru
Russian Federation, St. Petersburg

I. V. Shemarova

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences

Email: peep9@yandex.ru
Russian Federation, St. Petersburg

V. P. Nesterov

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences

Email: peep9@yandex.ru
Russian Federation, St. Petersburg

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2. Fig. 1. The effect of two different concentrations of Eu3+ (0.2 mM and 1 mM) on the contractions of the frog atria at a temperature of the washing solution of 20°C. (a) – the complete scheme of the experiment is shown; (b) – single contractions corresponding to contractions marked with black circles in the complete scheme of the experiment. W – washing of the atria from Eu3+. The concentrations of Eu3+ and the duration of incubation with Eu3+ are marked with a horizontal line under the contractions. The horizontal marks in the upper right indicate time in min (a), milliseconds (b). The force developed by the atria is calibrated with a vertical mark in milliNewtons (mN).

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3. Fig. 2. Effect of NaN3 on frog atrial contractions at a washing solution temperature of 20°C. Shown are the complete experimental schemes (a, c) and the corresponding single contractions (b, d), marked with black circles on the complete experimental scheme. (a) – control contraction, (c) – contraction after application of 0.2 mM Eu3+; 20 min after washing the atrium from 0.2 mM Eu3+, 1 mM NaN3 was added. The concentration of NaN3 and the duration of incubation with NaN3 are marked with a horizontal line under the contractions. The horizontal marks in the upper right indicate time, seconds (a, c), milliseconds (b, d). The force developed by the atria is calibrated with a vertical mark (mN).

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4. Fig. 3. Effect of Eu3+ and Ca2+ on the rate of oxygen consumption by rat heart mitochondria. Mitochondria (1 mg/ml protein) were added to the medium containing 125 mM KCl, 20 mM Tris-MOPS (pH 7.3) and 3 mM Tris-PO4, as well as (where indicated) 10 mM glutamate with 2 mM malate (G+M), 5 mM succinate with 2 μM rotenone (Succ), 50 μM Eu3+ (Eu3+) and 200 μM Ca2+ (Ca2+). The ordinate axis shows the rates of oxygen consumption (nmol O2/min/mg protein) in state 3 and state 3RDNP. To induce state 3 and state 3UDNP, the substances were successively added to the medium containing energized rat heart mitochondria to concentrations of 130 μM ADP and 30 μM DNP. State 3 and State 3UDNP are shown under the abscissa. Asterisks mark significant differences from the control, experiments without Eu3+ and Ca2+ (p < 0.05, paired t-test). The average results for three independent experiments are presented.

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