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


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.


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


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.


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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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