Українська English

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(6): 52-59

Peculiarities of the influence of mitochondrial ATP-dependent K+ channels activation on the function of external respiration under experimental pneumonia

P.K. Tsapenko1, A.S. Shapovalova1, О.G. Timchenko3, A.N. Golovko2, E.V. Rozova1, A.G. Portnichenko1

  1. Bogomoletz Institute of Physiology NAC of Ukrain, Kyiv, Ukraine
  2. Kyiv City Medical Special College, Kyiv, Ukraine
  3. Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine


The studies were performed on male Wistar rats weighing 250-270 with experimental pneumonia (EP) induced by the method of A.M. Kulik. The animals were divided into the following groups: 1 – control; 2 - experimental pneumonia; 3 (first experimental group) - animals, which in parallel with the simulation of pneumonia were intraperitoneally administered uridine at a dose of 0.3 mg/100 g of body weight (daily within 1 week); 4 (second experimental group) - animals in which uridine was administered daily starting from day 4 (at the peak of pneumonia). Animals with EP were examined at 5th (n = 10), 9th (n = 8) and 12th (n = 6) days of the disease development, as well as 1 (n = 5) and 2 (n = 5) months after EP modeling. It was shown that in the first experimental group on the 5th day of EP development, an isoventilator restructuring of respiration was observed. In this group, from day 12 to the end of the study, there was a stenoventilator restructuring of breathing, which was characterized by an increase in tidal volume, alveolar ventilation, oxygen consumption and, accordingly, an increase in oxygen extraction from the alveoli and in the oxygen effect of the respiratory cycle. It can be assumed that in this group, an increase in the intensity of metabolism is provided by the effective activity of the respiratory system. In the second experimental group, isoventilator changes in respiration were observed with a gradual decrease in oxygen consumption and other indicators of the respiratory system efficiency. After 2 months, these changes became significant. Thus, we can talk about significant differences in the effect of uridine on the function of external respiration (i.e., apparently, on the activity of the mitochondrial ATP-dependent K+ channel) during EP, which depended on the period of onset of uridine administration. Application of uridine immediately (1st experimental group) looks more effective and even has a stimulating effect on the respiratory function over a long period of experiment. The administration of uridine starting from the 4 partially normalizes the respiration parameters. However, after 1 month there is a depression of the functions of the respiratory system, which, probably, may further worsen. The reasons for the differences in the identified dynamics require further investigation.

Keywords: experimental pneumonia; uridine; external respiration; respiratory rate; tidal volume; oxygen consumption; respiratory efficiency.


  1. 10 leading causes of death in the world. 2020. [Electronic resource] - Access mode: room/fact-sheets/detail/the-top-10-causes-of-death [Russian].
  2. Macdonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth. 2003;90 (2): 221-32. CrossRef PubMed
  3. Bochkov VN, Kadl A, Huber J, et al. Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature. 2002;419 (6902):77-81. CrossRef PubMed
  4. Blackwell TS, Blackwell TR, Holden ER, et al. In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neu-trophilic lung inflammation. J Immunol. 1996;157 (4):1630-37.
  5. Schlieffen E, Oskolkova OV, Schabbauer G, et al. Multi-hit inhibition of circulating and cell-associated components of the toll-like receptor 4 pathway by oxidized phospholipids, Arterioscler. Thromb Vascul Biol. 2009;29 (3):356-62. CrossRef PubMed
  6. Mironova GD, Negoda AE, Marinov BS, et al. Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR). J Biol Chem. 2004;279 (31):4127-35. CrossRef PubMed
  7. Krylova IB, Kachaeva EV, Rodionova OM, et al. The cardioprotective effect of uridine and uridine-5'- monophosphate: the role of the mitochondrial ATP- dependent potassium channel. Exp Gerontol. 2006;41 (7): 697-703. CrossRef PubMed
  8. Krylova IB, Bul'on VV, Selina EN, et al. Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency. Bull Exp Biol Med. 2012;153 (5):644-6. CrossRef PubMed
  9. Yang C, Yuk J, Kim J, et al. Small heterodimer partner- targeting therapy inhibits systemic inflammatory responses through mitochondrial uncoupling protein. PLoS One. 2013;8 (5):1-15. CrossRef PubMed PubMedCentral
  10. Wojtovich AP, Williams DM, Karcz MK, et al. A novel mitochondrial K(ATP) channel assay. Circ Res. 2010;106 (7):1190-6. CrossRef PubMed PubMedCentral
  11. Connolly GP, Duley JA. Uridine and its nucleotides: biological actions, therapeutic potentials. TIPS. 1999;20(5):218-25. CrossRef
  12. Mironova GD, Rozova EV, Belosludtseva NV, Man'kovs- kaya IN. Dynamic restructuring of the myocardial mitochondria in response to uridine modulation of the activity of mitochondrial atp-dependent potassium channel under conditions of acute hypoxic hypoxia. Bull Exp Biol Med. 2019;166 (6):806-10. CrossRef PubMed
  13. Rozova EV, Mankovskaya IN, Belosludtseva NV, et al. Uridine as a protector against hypoxia-induced lung injury. Sci Rep. 2019;9 (1):9418. CrossRef PubMed PubMedCentral
  14. Mokhort MA, Seredynska NM, Kyrychok LM, et al. Pharmacological cjrrection of external breathing in the conditions of experimental pneumonia. Ukr Pulmonol J. 2008;(1): 61-5. [Ukranian].
  15. Barnard EA, Simon J, Webb TE. Nucleotide receptors in the nervous system. An abundant component using diverse transduction mechanisms. Mol Neurobiol. 1997;15 (2):103-29. CrossRef PubMed
  16. Shalbuyeva N, Brustovetsky T, Bolshakov A, Brustovetsky N. Calcium-dependent spontaneously reversible remodeling of brain mitochondria. J Biol Chem. 2006;281(49):37547-58. CrossRef PubMed
  17. Kulik AM. Regulation of respiration and pulmonary circulation in experimental pneumonia. Pathol Physiol General Patol. 1986;101 (2):144-7. [Russian]. CrossRef
  18. Voitkovskaya KS, Chernyaev AL. Acute lung injury syndrome: definition, pathogenesis, experimental models and the role of mesenchymal stem cells in the treatment of animals. Bull Modern Clin Med. 2012;5(2):60-7. [Russian].
  19. Shigaeva MI, Mironova GD. The role of the mitoKatf channel in physiology and pathology. Saarbrucken: LAP LAMBERT Acad Publ, Germany, 2010. [Russian].
  20. Rozova EV, Tavolzhanova TI. Influence of the morpho- functional state of the tissues of the lungs and heart on the main parameters of external respiration, blood circulation and gas exchange in hypoxic conditions of various types. General Pathol Pathol Physiol. 2010;5(3):09-13. [Russian].
  21. Lukyanova EM, Antipkin YuG, Chernyshov VP, Vykho- vanets EV. Methods of statistical processing of medical information in scientific research. Kiev: Planet of people, 2002. [Russian].
  22. Piper AJ, Yee BJ. Hypoventilation syndromes. Compr Physiol. 2014;4(4):1639-76. CrossRef PubMed
  23. Mironova GD, Khrenov MO, Talanov EYu, et al. The role of mitochondrial KATP channel in anti-inflammatory effects of uridine in endotoxemic mice. Arch Biochem Biophys. 2018;654(15):70-6. CrossRef PubMed
  24. Sosnovsky VV, Pastukhova VA, Ilyin VM. Chatacteristics of functional states of regulatory systems of the body in middle-distance runners with long-term adaptation to the conditions of the middle mountains. Fiziol Zh. 2018; 64(6); 55-62. [Ukrainian]. CrossRef

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.