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Effect of Sodium Ions on Calcium-Loaded Rat Heart Mitochondria and Frog Myocardium

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Abstract

The effect of calcium load on rat heart mitochondria [RHM(K+)], in which K+ ions in the matrix were partially replaced by Na+ ions [RHM(Na+)], was comparatively investigated. Calcium loading of RHM(K+) decreased their 2,4-dinitrophenol-uncoupled respiration and reduced the inner membrane potential (ΔΨmito). Swelling of these mitochondria increased in media with 25 mM potassium acetate or 125 mM NH4NO3. These effects of calcium loading were even greater in similar experiments with RHM(Na+). Inhibitors of the mitochondrial permeability transition pore (MPTP), ADP and cyclosporin A (CsA), abolished the above effects of Ca2+ completely in experiments with RHM(K+) and partially in experiments with RHM(Na+). A positive inotropic effect was observed with an increase in the extracellular concentration of Na+, however pre-incubation in a calcium-free solution led to a negative inotropic effect. Thus, partial replacement of K+ by Na+ in the matrix made rat heart mitochondria more sensitive to Ca2+ and increased the probability of MPTP opening in their inner membrane. Along with an elevation of cytoplasmic [Na+]i, this can further increase calcium overload of cardiomyocytes, making their damage during ischemia/reperfusion more likely.

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Abbreviations

CsA:

cyclosporin А

[Ca2+]i :

intracellular calcium concentration

[Ca2+]m :

matrix calcium concentration

[Na+]i :

intracellular sodium concentration

ΔΨmito :

inner membrane potential

IMM:

inner mitochondrial membrane

DNP:

2,4-dinitrophenol

RHM:

rat heart mitochondria

MPTP:

mitochondrial permeability transition pore

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ACKNOWLEDGMENTS

The authors are grateful to I.V. Brailovskaya for her assistance in isolating mitochondria and polarographic measuring mitochondrial oxygen uptake rates, L.V. Emelyanova for his help in determining the mitochondrial inner membrane potential of rat heart mitochondria, and A.I. Burdygin for creating a program for recording and processing of myocardial contraction data. Studies on determining the mitochondrial inner membrane potential were carried out at the Center for Collective Use at the Sechenov Institute of Evolutionary Physiology and Biochemistry.

Funding

This work was supported by the federal budget the Russian Federation allotted to the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences for the implementation of the governmental assignment АААА-А18-118012290142-9.

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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. Shemarova & 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. Shemarova
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Contributions

S.M.K.—conceptualization, experimental design, studies of mitochondrial swelling, data collection and processing, writing and editing a manuscript; K.V.S.—studies of contractile characteristics of frog heart muscle preparations, as well as the involvement, together with V.P.N., I.V.Sh. and S.M.K., in data discussion.

Corresponding author

Correspondence to S. M. Korotkov.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2021, Vol. 57, No. 6, pp. 484–493https://doi.org/10.31857/S0044452921060073.

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Korotkov, S.M., Sobol, K.V., Shemarova, I.V. et al. Effect of Sodium Ions on Calcium-Loaded Rat Heart Mitochondria and Frog Myocardium. J Evol Biochem Phys 57, 1241–1250 (2021). https://doi.org/10.1134/S0022093021060041

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