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Regulation of mitochondrial contact sites in neonatal, juvenile and diabetic hearts

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Abstract

Mitochondrial contact sites (MiCS) are dynamic structures involved in high capacity transport of energy from mitochondria into the cytosole. Previous studies revealed that in normal conditions the actual number of MiCS is in correlation with the energy requirements of the heart, particularly with those for its contractile work. Although the detailed mechanisms of signalling between the processes of energy utilisation and MiCS formation in the heart are not yet elucidated, it is known that intracellular Ca2+ transients are intimately involved in this crosstalk. The present study is devoted to investigation of Ca2+-linked MiCS formation in healthy adult hearts and in hearts with modified Ca2+-handling such as in developing, in juvenile and diabetic myocardium. Experiments were performed on hearts of healthy rats on the 22nd embryonal day, 1st, 4th, 7th and 14th postnatal days as well as on adult hearts. Diabetic hearts were investigated on the 8th day after streptozotocin injection (45 mg.kg–1 i.v.) to adult rats. Intracellular Ca2+ movements were affected by modulation of Ca2+ concentration in perfusion solution (1.6 or 2.2 mmol.l–1) in isolated, Langendorff-perfused hearts, by calcium paradox (CaP) or by replacing of Ca2+ by Cd2+ ions. Elevation of extracellular Ca2+ was reflected by 30.1, 10.4 and 24.1% increase in intracellular free Ca2+ concentration in healthy adult, diabetic and 14-day old hearts respectively. In developing hearts the amount of MiCS was culminating on the 4th postnatal day. In adult hearts, elevated calcium in the perfusion solution, CaP as well as diabetes led to a significant increase in the amounts of MiCS formed (58.1, 77.2 and 86.5% respectively; p < 0.05). Diabetic and 14-day old hearts naturally exhibited amounts of MiCS comparable to those obtained by Ca2+-stimulation of MiCS formation in adult healthy hearts. In contrast to healthy controls, perfusion of diabetic and 14-day old hearts with elevated Ca2+ as well as induction of CaP exerted little influence on MiCS formation (4.4 and 8.2% for elevated Ca2+; 2.9 and 10.7% for CaP; p > 0.05). A replacement of Ca2+ by Cd2+ ions lowered the amount of MiCS in healthy adult and diabetic hearts (61 and 52.2%; p < 0.05). In conclusion, during development, the formation of MiCS may be influenced by both, permanent stimulation by Ca2+-signalling and the availability of mCPK. In healthy adult hearts the amount of MiCS is modulated by intracellular Ca2+ transients in response to changes in extracellular Ca2+ concentration. In diabetic hearts the modulation of MiCS formation is naturally attenuated, apparently as a consequence of persisting alterations in Ca2+-handling.

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Authors and Affiliations

  1. Mgr. Institute for Heart Research, Slovak Academy of Sciences, Dúbravská cesta 9, 842 33, Bratislava, Slovak Republic

    Barbara Ziegelhöffer-Mihalovičová

  2. Carl-Ludwig-Institute, University of Leipzig, Liebigstr. 27, 041 03, Leipzig, Germany

    Barbara Ziegelhöffer-Mihalovičová

  3. Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic

    Attila Ziegelhöffer, Tanya Ravingerová & Narcis Tribulová

  4. Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    František Kolář

  5. Laboratory of Electron Microscopy, University of Antwerp, Antwerp, Belgium

    Wim Jacob

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Ziegelhöffer-Mihalovičová, B., Ziegelhöffer, A., Ravingerová, T. et al. Regulation of mitochondrial contact sites in neonatal, juvenile and diabetic hearts. Mol Cell Biochem 236, 37–44 (2002). https://doi.org/10.1023/A:1016189808285

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