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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

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. 2021; 67(1): 16-23


Yu.V. Danylovych, H.V. Danylovych, S.O. Kosterin

    Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, Kyiv, Ukraine


The NO-synthase activity (mtNOS) in mitochondria of uterine smooth muscle was studied. The mitochondrial localization of NO synthesis in myocytes was proved using laser confocal microscopy method and specific fluorescent probes MitoTracker Orange (specific to mitochondria) and DAFFM (NO-sensitive fluorescent probe). It was demonstrated using flow cytometry that nitric oxide biosynthesis in isolated mytochondria decreased in the presence of a constitutive NOsynthase blocker 2-aminopyridine (100 μmol per l, 50% inhibition) and monoclonal antibodies (2.5 μg anti-Let m1 per 50 μg protein) against the H+-Ca2+-exchanger (Letm1 protein), but was’t sensitive to the mitochondrial permeability transition pore inhibitor cyclosporin A (5 μmol per l). A decrease of potassium ions concentration in the incubation medium and the presence of various types of potassium channel inhibitors significantly inhibited the NO-synthase reaction. We have concluded that potassium permeability of the inner mitochondrial membrane plays important role in the regulation of mtNOS activity.

Keywords: nitric oxide; mitochondria; potassium channels; mtNOS; smooth muscle


  1. Fernando V, Zheng X, Walia Y, Sharma V, Letson J, Furuta S S-Nitrosylation: An emerging paradigm of redox signaling. Antioxidants. 2019;8:404. CrossRef PubMed PubMedCentral
  2. Giulivi C. Mitochondria as generators and targets of nitric oxide. Novartis Found Symp. 2007;287:92-104. CrossRef PubMed
  3. Zaobornyj T, Ghafourifar P. Strategic localization of heart mitochondrial NOS: a review of the evidence. Am J Physiol: Heart Circ Physiol. 2012;303(11):H1283-93. CrossRef PubMed
  4. Traaseth N, Elfering S, Solien J, Haynes V, Giulivi C. Role of calcium signaling in activation of mitochondrial nitric oxide synthase and citric acid cycle. Biochim Biophys Acta. 2004;1658(1-2):64-71. CrossRef PubMed
  5. Levine AB, Punihaole D, Levine TB. Characterization of the role of nitric oxide and its clinical applications. Cardiology. 2012;122:55-68. CrossRef PubMed
  6. Davidson SM, Duchen MR. Effects of NO on mitochondrial function in cardiomyocytes: pathophysiological relevance. Cardiovascul Res. 2006;71(1):10-21. CrossRef PubMed
  7. Litvinova L, Atochin DN, Fattakhov N, Vasilenko M, Zatolokin P, Kirienkova E. Nitric oxide and mitochondria in metabolic syndrome. Front Physiol. 2015;6:20. CrossRef PubMed PubMedCentral
  8. Danylovych HV, Danylovych Yu V, Bohach TV, Hurska VT, Kosterin SO. Sources and regularity of nitric oxide synthesis in uterus smooth muscle cells. Ukr Biochem J. 2019;91(4):33-40. [Ukrainian]. CrossRef
  9. Vadziuk OB. ATP-sensitive K(+)-channels in muscle cells: features and physiological role. Ukr Biochem J. 2014;86(3):5-22. [Ukrainian]. CrossRef
  10. Szabo I, Zoratti M. Mitochondrial channels: ion fluxes and more. Physiol Rev. 2014;94(2):519-608. CrossRef PubMed
  11. Kaasik A, Safiulina D, Zharkovsky A, Veksler V. Regulation of mitochondrial matrix volume. Am J Physiol Cell Physiol. 2007;292:C157-C63. CrossRef PubMed
  12. Nowikovski K, Schweyen RJ, Bernardi P. Pathophysiology of mitochondrial volume homeostasis: potassium transport and permeability transition. Biochim Biophys Acta. 2009;1787(5):345-50. CrossRef PubMed
  13. Strutyns'ka NA, Strutyns'kyĭ RB, Chorna SV, Semenykhina OM, Mys'LA, Moĭbenko OO, Sahach VF. New fluorine-containing openers of ATP-sensitive potassium channels flokalin and tioflokalin inhibit calcium-induced mitochondrial pore opening in rat hearts. Fiziol Zh. 2013;59(6):3-11. [Ukrainian].
  14. Danylovych Yu V, Chunikhin AY, Danylovych GV, Kolomiets OV. The use of the Petri net method in the simulation modeling of mitochondrial swelling. Ukr Biochem J. 2016;88(4):66-74. [Ukrainian]. CrossRef PubMed
  15. Leite ACR, Oliveira HCF, Utino FL, Garcia R, Alberici LC, Fernandes MP, Castilho RF, Vercesi AE. Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols. Biochim Biophys Acta. 2010;1797(6-7):1210-16. CrossRef PubMed
  16. Mollard P, Mironneau J, Amedee T, et al. Electrophysiological characterization of single pregnant rat myometrial cells in short-term primary culture. Am J Physiol Cell Physiol. 1986;250(1):C47-C54. CrossRef PubMed
  17. Kosterin S.A, Bratkova NF, Kurskii MD. The role of sarcolemma and mitochondria in calcium-dependent control of myometrium relaxation. Biochemistry. 1985;50(8):1350-61. [Russian].
  18. Dedkova EN, Blatter LA. Characteristics and function of cardiac mitochondrial nitric oxide synthase. J Physiol. 2009; 587(Part 4):851-72. CrossRef PubMed PubMedCentral
  19. Franco MC, Antico Arciuch VG, Peralta JG, Galli S, Levisman D, Lopez LM, Romorini L, Poderoso JJ, Carreras MC. Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase. J Biol Chem. 2006; 281(8): 4779-86. CrossRef PubMed
  20. Lawton GR, Ranaivo HR, Chico LK, Ji H, Xue F, Martásek P, Roman LJ, Watterson DM, Silverman RB. Analogues of 2-aminopyridine-based selective inhibitors of neuronal nitric oxide synthase with increased bioavailability. Bioorg Med Chem. 2009;17(6):2371-80. CrossRef PubMed PubMedCentral
  21. Кolomiets ОV, Danylovych YuV, Danylovych GV, Kosterin SО. Ca2+ accumulation study in isolated smooth muscle mitochondria using Fluo-4 AM. Ukr Biokhim Zh. 2013;85(4):30-9. [Ukrainian]. CrossRef PubMed
  22. Kolomiets OV, Danylovych YuV, Danylovych GV. H+-Ca2+ exchanger in the myometrium mitochondria: Modulation by exogenous and endogenous compounds. Int J Phys Pathophys. 2015;6(4):287-97. CrossRef
  23. Strutyns'ka NA, Semenykhina OM, Chorna SV, Vavilova HL, Sahach VF. Hydrogen sulfide inhibits Ca2+-induced mitochondrial permeability transition pore opening in adult and old rat heart. Fiziol Zh. 2011;57(6):3-14. [Ukrainian]. CrossRef
  24. Shao J, Fu Z, Ji Y, Guan X, Guo S, Ding Z, Yang X, Cong Y, Shen Y. Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter. Sci Rep. 2016;6:341-74. CrossRef PubMed PubMedCentral
  25. Walewska A, Szewczyk A, Koprowski P. Gas signaling molecules and mitochondrial potassium channels. Int J Mol Sci. 2018;19(10):3227. CrossRef PubMed PubMedCentral
  26. Bai Y, Murakami MH, Iwasa M, Sumi S, Yamada Y, Ushikoshi H, Aoyama T, Nishigaki K, Takemura G, Uno B, Minatoguchi S. Cilostazol protects the heart against ischemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels. Clin Exp Pharmacol Physiol. 201;38(10):658-65. CrossRef PubMed

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