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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2014; 60(5): 73-81

The role of mitochondrial uniporter in calcium-homeostasis of the exorbital lacrimal gland secretory cells

Kotliarova AB1,2, Merlavs'kyĭ VM1, Dorosh OM1, Man'ko VV1

  1. Ivan Franko National University of L`viv, Ukraine
  2. Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz60.05.073


Abstract

The role of mitochondrial calcium-uniporter in calciumhomeostasis maintenance and correlations of calciumuniporter with other calcium-transport systems of the rat exorbital lacrimal gland secretory cells were studied. The experiments were performed on intact and digitoninpermeabilized cells. The interdependence of calciumuniporter and other calcium-transporting systems functioning was estimated on the basis of additivity of their inhibitors/agonists effects, which was accompanied with a decrease in the Ca2+ content in the gland cells. It was found that in conditions of simultaneously inhibition of sarco endoplasmic reticulum „Ra2+-ATPase (SERCA) and mitochondrial calcium-uniporter Ca2+ passively released from different calcium stores, because the effects of these calcium-transport systems inhibitors (thapsigargin and ruthenium red, respectively) were additive. Similarly, the processes of inositol-1,4,5-trisphosphate receptors (IP3Rs) activation and Calcium-uniporter inhibition were additive. In contrast, the effects of ryanodine and ruthenium red on the Ca2+ content in cells were significantly non-additive. In addition, ryanodine at concentrations 1.3 ѓК„M reduced respiration rate of studied cells in dose-dependent manner, and this effect was persisted at cells preincubation with ruthenium red or tapsigargin. Thus, besides the activation of ryanodine receptors (RyRs) in endoplasmic reticulum, ryanodine inhibits Ca2+ influx to the mitochondrial matrix, that was insensitive to ruthenium red. Key words: Calcium-uniporter of mitochondria, ruthenium red, sarcoendoplasmic reticulum „Ra2+-ATPase (SERCA), inositol-1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs), lacrimal glands, secretory cells.

Keywords: Calcium-uniporter of mitochondria, rutheniumred, sarcoendoplasmic reticulum Сa2+-ATPase (SERCA),inositol-1,4,5-trisphosphate receptors (IP3Rs), ryanodinereceptors (RyRs), lacrimal glands, secretory cells.

Full text: (PDF, in Ukrainian)

References

  1. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012;13(9):566–78. CrossRef PubMed
    2.  
  2. Zimmermann B. Control of InsP3-induced Ca2+ oscillations in permeabilized blowfly salivary gland cells: contribution of mitochondria. J Physiol. 2000;525(3): 707–19. CrossRef PubMed PubMedCentral
    3.  
  3. Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highlyselective ion channel. Nature. 2004;427(6972):360–4. CrossRef PubMed
    4.  
  4. Griffiths EJ. Use of ruthenium red as an inhibitor of mitochondrial Ca2+ uptake in single rat cardiomyocytes. FEBS Lett. 2000; 486(3):257–60. CrossRef  
  5. Bird G St J, Obie JF, and Putney JW Jr. Functional homogeneity of the non-mitochondrial Ca2+ pool in intact mouse lacrimal acinar cells. Biol Chem Journ. 1992;267(26):18382–86.
    6.  
  6. Herzog V, Sies H, Miller F. Exocytosis in secretory cells of rat lacrimal gland. Peroxidase release from lobules and isolated cells upon cholinergic stimulation. J Cell Biol. 1976;70:692–706. CrossRef PubMed
    7.  
  7. Kotliarova A, Manko V. Permeabilized secretory cells of rats exorbital lacrimal glands as a model for Sa2+-transport systems study. Bulletin of Taras Shevchenko National University of Kyiv Biological series. 2013;64(2):11–5.
    8.  
  8. Kotliarova AB, Manko VV. IP3-sensitive Ca2+-channels of endoplasmic reticulum in secretory cells of the rat exorbital lacrimal gland. Ukr Biochem Journ. 2013;85(5):27–36. [Ukrainian]. CrossRef  
  9. Kotliarova AB, Manko VV. Ca2+ transporting systems in secretory cells of the rat exorbital lacrimal gland I Ca2+ pumps of plasma membrane and endoplasmic reticulum. Studia Biologica. 2012;6(2):99–114. [Ukrainian].
    10.  
  10. Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K. 2APB, 2-Aminoethoxydiphenyl borate, a membranepenetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem. 1997;122(3):498–505. CrossRef PubMed
    11.  
  11. Kotliarova A., Manko V. Effect of 2-APB on SERCA of lacrimal gland secretory cells. Exp Clin Physiol Biochem. 2013;(3):38–43. [Ukrainain].
    12.  
  12. Ozawa T. Ryanodine-sensitive Ca2+ release mechanism in non-excitable cells. Int J Mol Med. 2001;7(1):21–5. CrossRef  
  13. Beutner G, Sharma VK, Giovannucci D, Yule D, Sheu S-S. Identification of a ryanodine in receptor in rat heart mitochondria. J Biol Chem. 2001;276(24):21482–8. CrossRef PubMed
    14.  
  14. Altschafl BA, Beutner G, Sharma VK, Sheu SS, Valdivia HH. The mitochondrial ryanodine receptor in rat heart: a pharmaco-kinetic profile. Biochim Biophys Acta. 2007;1768(7):1784–95. CrossRef PubMed
    15.  
  15. Buck E, Zimanyi I, Abramson JJ, Pessah IN. Ryanodine stabilizes multiple conformational states of the skeletal muscle calcium release channel. J Biol Chem. 1992; 267:23560–7. PubMed
    16.  
  16. Denton RM, McCormack JG. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 1980;119(1):1–8. CrossRef  
  17. Brand DM, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J. 2011;435:297–312. CrossRef PubMed PubMedCentral
    18.  
  18. Kohlhaas M, Maack Ch. Calcium release microdomains and mitochondria. Cardiovasc Res. 2013;98(2):259–68. CrossRef PubMed
    19.  
  19. Rizzuto R, Pinton P, Carrington W, Fay F, Fogarty K, Lifshitz L et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998;280(5370):1763–66. CrossRef PubMed
    20.  
  20. Hajnoczky G, Hager R, Thomas AP. Mitochondria suppress local feedback activation of inositol 1,4,5-trisphosphate receptors by Ca2+. J Biol Chem. 1999;274:14157–62. CrossRef PubMed
    21.  
  21. Vallot O, Combettes L, Lompre A-M. Functional coupling. B. Kotlyarova, V.M. Merlavs'kii, O.M. Dorosh, V.V. Man'ko between the caffeine/ryanodine-sensitive Ca2+ store and mitochondria in rat aortic smooth muscle cells. Biochem J. 2001;357(Pt 2):363–71. CrossRef PubMed PubMedCentral
    22.  
  22. Sharma VK., Ramesh V, Franzini-Armstrong C, Sheu S-S. Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes. J Bioenerg Biomembr. 2000;32(1):97–104. CrossRef  
  23. Montero M, Alonso M, Carnicero E, Cuchillo-Ibanez I, Albillos A, Garcia A et al. Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion. Nat Cell Biol. 2000;2(2):57–61. CrossRef PubMed
    24.  
  24. Kotliarova AB, Manko BO, Manko VV. The effect of carbacholine on respiration of the rat exorbital lacrimal cells. Actual problems of Humanities and Sciences. 2013:12(2):41–3. [Russian].
    25.  

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