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L-type Ca2+ channels’ involvement in IFN-γ-induced signaling in rat ventricular cardiomyocytes

  • Vadim Mitrokhin
  • Tatiana Filatova
  • Andrey Shim
  • Andrey Bilichenko
  • Denis Abramochkin
  • Andre Kamkin
  • Mitko MladenovEmail author
Original Article

Abstract

The purpose of this study was to examine the effects of interferon-γ (IFN-γ) on calcium movement in rat ventricular myocytes. L-type Ca2+ currents (ICa,L) were recorded with the whole-cell configuration of the patch-clamp techniques. IFN-γ induces current density reduction at the test potential of 0 mV by 47.6 ± 7.4%. Heparin, a selective inhibitor of inositol-1,4,5-triphosphate (IP3)–induced Ca2+ release, applied via a patch pipette, induced an ICa,L amplitude decrease of about 46 ± 5.6%. The addition of IFN-γ to heparin-treated cells has no effect on ICa,L. Ryanodine induced an ICa,L current amplitude decrease of 35.1 ± 6.2%. The addition of IFN-γ to ryanodine-treated cells caused an additional ICa,L inhibiting of 17.6 ± 4.8%. Both cyclopiazonic acid (CPA), a specific SERCA inhibitor, and a combination of CPA and ryanodine caused a significant reduction of the ICa,L amplitudes. Subsequent addition of IFN-γ inhibited ICa,L for an additional 16.3 ± 4.4%. The employment of chelerythrine in this study prevented IFN-γ-induced L-type Ca2+ channel inhibition in only 10 min from the start of perfusion. Proposed mechanisms of regulation involved IFN-γ-induced IP3-sensitive Ca2+ release probably by a Ca2+-dependent translocation of PKC from the cytoplasm to the cell membrane as the obligatory first step of the IFN-γ-induced PKC-dependent L-type Ca2+ channel inhibition.

Keywords

Cytokine Interferon-γ L-type Ca2+ channels Store-operated Ca2+ entry Ventricular cardiomyocytes Rat 

Notes

Author contributions

All authors contributed toward data analysis, drafting, and revising the paper and agree to be accountable for all aspects of the work.

Funding information

This work was supported by the Russian Science Foundation (grant no. 16-14-10372).

Compliance with ethical standards

All procedures were approved by the Local Bioethical Committee for Animal Care (permission no. 3/2014).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Aas V, Larsen K, Iversen JG (1998) IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils. J Interf Cytokine Res 18:197–205CrossRefGoogle Scholar
  2. 2.
    Aksyonov A, Mitrokhin VM, Mladenov MI (2015) Effects of interleukin-2 on bioelectric activity of rat atrial myocardium under normal conditions and during gradual stretching. Immunol Lett 167:23–28CrossRefGoogle Scholar
  3. 3.
    Bechem M, Pott L (1985) Removal of Ca2+ current inactivation in dialyzed guinea-pig atrial cardioballs by Ca2+ chelators. Pflugers Arch 404:10–20Google Scholar
  4. 4.
    Bers D (2013) Membrane receptor neighborhoods: snuggling up to the nucleus. Circ Res 112:224–226CrossRefGoogle Scholar
  5. 5.
    Borda E, Leiros CP, Sterin-Borda L, de Bracco MM (1991) Cholinergic response of isolated rat atria to recombinant rat interferon-gamma. J Neuroimmunol 32:53–59CrossRefGoogle Scholar
  6. 6.
    Deb DK, Sassano A, Lekmine F, Majchrzak B, Verma A, Kambhampati S, Uddin S, Rahman A, Fish EN, Platanias LC (2003) Activation of protein kinase C delta by IFN-gamma. J Immunol 171:267–273CrossRefGoogle Scholar
  7. 7.
    Filatova T, Mitrokhin V, Kamkina O, Lovchikova I, Mladenov M, Kamkin A (2018) Long-term IL-2 incubation-induced L-type calcium channels activation in rat ventricle cardiomyocytes. Cardiovasc Toxicol.  https://doi.org/10.1007/s12012-018-9472-0
  8. 8.
    Ghigo A, Laffargue M, Li M, Hirsch E (2017) PI3K and calcium signaling in cardio- vascular disease. Circ Res 121:282–292CrossRefGoogle Scholar
  9. 9.
    Haack AJ, Rosenberg LR (1994) Calcium-dependent inactivation of L-type calcium channels in planar lipid bilayers. Biophys J 66:1051–1060CrossRefGoogle Scholar
  10. 10.
    Hadley RW, Lederer WJ (1991) Ca2+ and voltage inactivate Ca2+ channels in guinea-pig ventricular myocytes through independent mechanisms. J Physiol 444:257–268CrossRefGoogle Scholar
  11. 11.
    Hohendanner F, McCulloch DA, Blatter AL, Michailova PA (2014) Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches. Front Pharmacol 6(5):35Google Scholar
  12. 12.
    Ibarra CC, Vicencio JM, Estrada M, Lin Y, Rocco P, Rebellato P, Munoz JP, Garcia-Prieto J, Quest AFG, Chiong M, Davidson SM, Bulatovic I, Grinnemo KH, Larsson O, Szabadkai G, Uhlén P, Jaimovich E, Lavandero S (2013) Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors. Circ Res 112:236–245CrossRefGoogle Scholar
  13. 13.
    Isenberg G, Klockner U (1982) Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium”. Pflugers Arch 395:6–18CrossRefGoogle Scholar
  14. 14.
    Kazanski V, Mitrokhin V, Mladenov MI, Kamkin AG (2017) Cytokine effects on mechano-induced electrical activity in atrial myocardium. Immunol Investig 46:22–37CrossRefGoogle Scholar
  15. 15.
    Levick PS, Goldspink HP (2014) Could interferon-gamma be a therapeutic target for treating heart failure. Heart Fail Rev 19:227–236CrossRefGoogle Scholar
  16. 16.
    Lipp P, Huser J, Pott L et al (1996) Spatially non-uniform Ca2+ signals induced by the reduction of transverse tubules in citrate-loaded guinea-pig ventricular myocytes in culture. J Physiol Lond 497:589–597CrossRefGoogle Scholar
  17. 17.
    Lu Z, Jiang YP, Wang W, Xu XH, Mathias RT, Entcheva E, Ballou LM, Cohen IS, Lin RZ (2009) Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction. Circulation 120:318–325Google Scholar
  18. 18.
    Mitrokhin MV, Mladenov IM, Kamkin GA (2015) IL-1 provokes electrical abnormalities in rat atrial myocardium. Int Immunopharmacol 28:780–784CrossRefGoogle Scholar
  19. 19.
    Mitrokhin VM, Mladenov MI, Kamkin AG (2015) Effects of interleukin-6 on the bio-electric activity of rat atrial tissue under normal conditions and during gradual stretching. Immunobiology 220:1107–1112CrossRefGoogle Scholar
  20. 20.
    Mitrokhin V, Mladenov M, Gorbacheva L, Babkina I, Lovchikova I, Kazanski V, Kamkin A (2018) Influence of NO and [Ca2+]o on [Ca2+]i homeostasis in rat ventricular cardiomyocytes. Biotechnol Biotechnol Equip:1–6.  https://doi.org/10.1080/13102818.2018.1488621
  21. 21.
    Mu Y-h, Zhao W-c, Duan P, et al (2014) RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes. PLoS One 9: e94905Google Scholar
  22. 22.
    Ovchinnikov RS, Mitrokhin VM, Mladenov MI (2015) Effects of interleukin-17A on the bioelectric activity of rat atrial myocardium under normal conditions and during gradual stretching. Cytokine 76:561–565CrossRefGoogle Scholar
  23. 23.
    Seo JY, Kim DY, Lee YS, Ro JY (2009) Cytokine production through PKC/p38 signaling pathways, not through JAK/STAT1 pathway, in mast cells stimulated with IFN-gamma. Cytokine 46:51–60Google Scholar
  24. 24.
    Steinberg SF (2012) Cardiac actions of protein kinase C isoforms. Physiology (Bethesda) 27:130–139Google Scholar
  25. 25.
    Wellmann GC, Nelson MT (2003) Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels. Cell Calcium 34:211–229CrossRefGoogle Scholar
  26. 26.
    Woodcock EA, Matkovich SJ (2005) Ins(1,4,5)P3 receptors and inositol phosphates in the heart-evolutionary artefacts or active signal transducers. Pharmacol Ther 107:240–251CrossRefGoogle Scholar

Copyright information

© University of Navarra 2019

Authors and Affiliations

  • Vadim Mitrokhin
    • 1
  • Tatiana Filatova
    • 2
  • Andrey Shim
    • 1
  • Andrey Bilichenko
    • 1
  • Denis Abramochkin
    • 2
    • 3
  • Andre Kamkin
    • 1
  • Mitko Mladenov
    • 1
    • 4
    Email author
  1. 1.Department of Fundamental and Applied PhysiologyRussian National Research Medical UniversityMoscowRussia
  2. 2.Department of Human and Animal PhysiologyBiological Faculty of the Moscow State UniversityMoscowRussia
  3. 3.Laboratory of Cardiac PhysiologyInstitute of Physiology, Komi Science Center, Ural Branch, Russian Academy of SciencesSyktyvkarRussia
  4. 4.Faculty of Natural Sciences and Mathematics, Institute of Biology“Ss. Cyril and Methodius” UniversitySkopjeMacedonia

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