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Effects of Gd3+ and Ca2+ on Frog Heart Muscle Contractility and Respiration, Swelling and Inner Membrane Potential of Rat Heart Mitochondria

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Abstract

We studied the inotropic and chronotropic effects of gadolinium ions (Gd3+) on contractility of frog Rana ridibunda heart muscle preparations. In addition, the influence of Gd3+ on oxygen uptake rates, swelling and the mitochondrial inner membrane potential (ΔΨmito) were studied in glutamate- and malate-energized rat heart mitochondria (RHM). It was found that Gd3+ decreases the amplitude and frequency of spontaneous heart contractions. At the same time, Gd3+ prevents Ca2+-induced swelling of these organelles in saline media and falling of ΔΨmito. In this case, regardless of the presence of Ca2+ in the medium, Gd3+ has a weak effect on mitochondrial state 3 or 3UDNP respiration (in the presence of 2,4-dinitrophenol). In calcium free experiments, Gd3+ stimulates passive swelling of RHM. These effects of Gd3+ may indicate that Gd3+ has no toxic effect on RHM but, on the other hand, inhibits opening of the mitochondrial permeability transition pore (MPTP) in the inner membrane. Our data provide better insight into the mechanisms of action of rare earth elements on Ca2+-dependent processes in the myocardium of vertebrates.

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Abbreviations

СаV :

voltage-gated Ca2+ channels

СaV1.2:

L-type voltage-gated Ca2+ channels

GBCAs:

gadolinium-based contrast agents

F max :

spontaneous heart contraction frequency

ΔΨmito :

mitochondrial inner membrane potential

IMM:

inner mitochondrial membrane

DNP:

2,4-dinitrophenol

CM:

cardiomyocytes

RHM:

rat heart mitochondria

MPTP:

Ca2+-dependent mitochondrial permeability transition pore

NSF:

nephrogenic systemic fibrosis

SAN:

sinoatrial node

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ACKNOWLEDGMENTS

Authors are grateful to I.V. Brailovskaya for her help in isolating mitochondria and polarographic measuring their oxygen uptake rates. Studies on determining a mitochondrial membrane potential were carried out on the basis of the Research Resource Center equipment at Sechenov Institute of Evolutionary Physiology and Biochemistry.

Funding

This work was supported by a state contract with the Federal Agency for Scientific Organizations of Russia (project no. AAAA-A18-118012290142-9).

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    S. M. Korotkov, K. V. Sobol, I. V. Schemarova, A. V. Novozhilov, E. R. Nikitina & V. P. Nesterov

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  1. S. M. Korotkov
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  2. K. V. Sobol
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  3. I. V. Schemarova
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  4. A. V. Novozhilov
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  5. E. R. Nikitina
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  6. V. P. Nesterov
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Correspondence to S. M. Korotkov.

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Korotkov, S.M., Sobol, K.V., Schemarova, I.V. et al. Effects of Gd3+ and Ca2+ on Frog Heart Muscle Contractility and Respiration, Swelling and Inner Membrane Potential of Rat Heart Mitochondria. J Evol Biochem Phys 56, 541–549 (2020). https://doi.org/10.1134/S0022093020060071

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