Moscow University Physics Bulletin

, Volume 73, Issue 5, pp 526–533 | Cite as

Clusterization of Inositol Trisphosphate Receptors Determines the Shape of the Calcium Oscillation Peak in Platelet Cytosol

  • F. A. BalabinEmail author
  • D. S. Morozova
  • A. S. Mayorov
  • A. A. Martyanov
  • M. A. Panteleev
  • A. N. Sveshnikova


Platelets, which are anucleate blood cells, should have the capacity to respond to an external stimulus within 1 second. This capacity is maintained by calcium signaling, the process of intracellular signal transmission mediated by an increase of the calcium ion concentration in the cytosol due to calcium release from the endoplasmic reticulum through the inositol trisphosphate receptor channel (IP3R). The increase of the calcium concentration in the platelet cytosol is not monotonous, but rather has an oscillatory character, similar to the processes in many other cell types. The regularities that underlie the development of these oscillations were subjected to theoretical and experimental analysis in the present study. Total internal reflection microscopy of platelets immobilized on fibrinogen and loaded with the Fura-2 calcium-sensitive fluorescent label was used to monitor the dynamics of calcium concentration. The mathematical model of the IP3R–ATPase pair from [15] modified to take the platelet parameters into account was used to describe the process of oscillation development. The results of the study demonstrated a characteristic peak shape for calcium oscillations in the platelet: theoretical description of the peak shape essentially required the introduction of corrections that had the physical meaning of cooperative IP3R activation.


blood platelets intracellular signaling thrombin inositol trisphosphate calcium signaling mathematical modeling fluorescence microscopy. 



The authors are grateful to the Corresponding RAS Member F.I. Ataullakhanov (CTP PCP RAS) for support and discussion of the data and to V.V. Mustyatsa (Rogachev NMRC PHOI) for technical support.

The work was supported by grant 17-74-20045 of the Russian Science Foundation.


  1. 1.
    A. D. Michelson, Platelets (Elsevier, 2013).Google Scholar
  2. 2.
    J. E. Purvis, M. S. Chatterjee, L. F. Brass, et al., Blood 112, 4069 (2008).CrossRefGoogle Scholar
  3. 3.
    L. Lian, Y. Wang, J. Draznin, et al., Blood 106, 110 (2005). doi 10.1182/blood-2004-05-2005CrossRefGoogle Scholar
  4. 4.
    A. N. Sveshnikova, F. I. Ataullakhanov, and M. A. Panteleev, Mol. Biosyst. 11, 1052 (2015). doi 10.1039/c4mb00667dCrossRefGoogle Scholar
  5. 5.
    D. Varga-Szabo, A. Braun, and B. Nieswandt, J. Thromb. Haemostasis 7, 1057 (2009).CrossRefGoogle Scholar
  6. 6.
    S. I. Obydennyy, A. N. Sveshnikova, F. I. Ataullakhanov, et al., J. Thromb. Haemostasis 14, 1867 (2016). doi 10.1111/jth.13395CrossRefGoogle Scholar
  7. 7.
    J. W. Heemskerk, J. Hoyland, W. T. Mason, et al., Biochem. J. 283, 379 (1992).CrossRefGoogle Scholar
  8. 8.
    M. Chalmers, M. J. Schell, and P. Thorn, Biochem. J.  394, 57 (2006). doi 10.1042/BJ20051130CrossRefGoogle Scholar
  9. 9.
    F. A. Balabin and A. N. Sveshnikova, Math. Biosci. 276, 67 (2016). doi 10.1016/j.mbs.2016.03.006MathSciNetCrossRefGoogle Scholar
  10. 10.
    S. S. Shakhidzhanov, V. I. Shaturny, M. A. Panteleev, et al., Biochim. Biophys. Acta, Gen. Subj. 1850, 2518 (2015). doi 10.1016/j.bbagen.2015.09.013CrossRefGoogle Scholar
  11. 11.
    A. N. Sveshnikova, A. V. Balatskiy, A. S. Demianova, et al., J. Thromb. Haemostasis 14, 2045 (2016). doi 10.1111/jth.I3442CrossRefGoogle Scholar
  12. 12.
    T. Mazel, R. Raymond, M. Raymond-Stintz, et al., Biophys. J. 96, 1691 (2009). doi 10.1016/j.bpj.2008.10.066ADSCrossRefGoogle Scholar
  13. 13.
    S. M. Jobe, K. M. Wilson, L. Leo, et al., Blood 111, 1257 (2008). doi 10.1182/blood-2007-05-092684CrossRefGoogle Scholar
  14. 14.
    B. L. van der Waerden, Mathematical Statistics (Springer, 1969).CrossRefzbMATHGoogle Scholar
  15. 15.
    G. W. De Young and J. Keizer, Proc. Natl. Acad. Sci. U. S. A. 89, 9895 (1992).ADSCrossRefGoogle Scholar
  16. 16.
    J. Keizer and G. W. De Young, J. Theor. Biol. 166, 431 (1994). doi 10.1006/jtbi.1994.1038CrossRefGoogle Scholar
  17. 17.
    J. Sneyd and M. Falcke, Prog. Biophys. Mol. Biol. 89, 207 (2005).CrossRefGoogle Scholar
  18. 18.
    A. Skupin and M. Falcke, in Proceedings of the 8th Annual International Workshop on Bioinformatics and Systems Biology, Berlin, Germany, 2008, Ed. by  E.‑W. Knapp, G. Benson, H.-G. Holzhütter, M. Kanehisa, and S. Miyano (Imperial College Press, 2008), p. 15. doi 10.1142/9781848163003_0002Google Scholar
  19. 19.
    A. Mees and L. Chua, IEEE Trans. Circuits Syst. 26, 235 (1979). doi 10.1109/TCS.1979.1084636CrossRefGoogle Scholar
  20. 20.
    J. W. Heemskerk, W. M. Vuist, M. A. Feijge, et al., Blood 90, 2615 (1997).Google Scholar
  21. 21.
    J. F. Hussain and M. P. Mahaut-Smith, J. Physiol. 514, 713 (1999).CrossRefGoogle Scholar
  22. 22.
    J. Keener and J. Sneyd, Mathematical Physiology II: Systems Physiology (Springer, New York, 2009). doi 10.1007/978-0-387-79388-7CrossRefzbMATHGoogle Scholar
  23. 23.
    J. Keener and J. Sneyd, Mathematical Physiology I: Cellular Physiology (Springer, New York, 2009), p. 273. doi 10.1007/978-0-387-75847-3_7CrossRefzbMATHGoogle Scholar
  24. 24.
    T. Rahman, Biochem. Soc. Trans. 40, 325 (2012). doi 10.1042/BST20110772CrossRefGoogle Scholar

Copyright information

© Allerton Press, Inc. 2018

Authors and Affiliations

  • F. A. Balabin
    • 1
    Email author
  • D. S. Morozova
    • 2
  • A. S. Mayorov
    • 1
    • 3
    • 4
  • A. A. Martyanov
    • 1
    • 3
    • 4
  • M. A. Panteleev
    • 1
    • 3
    • 4
  • A. N. Sveshnikova
    • 1
    • 3
    • 4
  1. 1.Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of SciencesMoscowRussia
  2. 2.Department of Fundamental Medicine, Moscow State UniversityMoscowRussia
  3. 3.Department of Physics, Moscow State UniversityMoscowRussia
  4. 4.Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and ImmunologyMoscowRussia

Personalised recommendations