Neurochemical Journal

, Volume 7, Issue 1, pp 29–33 | Cite as

Calcium-dependent phosphatase calcineurin downregulates evoked neurotransmitter release in neuromuscular junctions of mice

  • A. E. GaydukovEmail author
  • E. O. Tarasova
  • O. P. Balezina
Experimental Articles


We have shown in neuromuscular synapses of mice that inhibition of calcium- and calmodulin-dependent phosphatase calcineurin by cyclosporine A or calcineurin-inhibiting peptide results in a considerable increase in the quantum content of evoked endplate potentials (EPPs) during a short rhythmic train (50 Hz for 1 s). This increase was completely blocked by nitrendipine (a blocker of voltage-dependent calcium channels of the L-type) or inhibition of ryanodine receptors by TMB-8 or ryanodine. The quantum content of single EPPs increased in the presence of an activator of L-type calcium channels, S(-) Bay K 8644. In the presence of this drug, cyclosporine A was unable to further increase the quantum content of EPPs. We concluded that calcineurin during normal functioning of motor synapses of mice inhibits evoked secretion via a decrease in calcium influx via L-type channels and calcium release via ryanodine receptors from intracellular stores.


calcineurin evoked activity quantum content L-type calcium channels ryanodine receptors cyclosporine A 


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  1. 1.
    Klee, C. and Krinks, M., Biochemistry, 1978, vol. 17, pp. 120–126.PubMedCrossRefGoogle Scholar
  2. 2.
    Rusnak, F. and Mertz, P., Physiol. Rev., 2000, vol. 80, pp. 1483–1521.PubMedGoogle Scholar
  3. 3.
    Yakel, J., Trends Pharmacol. Sci., 1997, vol. 18, pp. 124–134.PubMedCrossRefGoogle Scholar
  4. 4.
    Marks, B. and McMahon, H., Curr. Biol, 1998, vol. 8, pp. 740–749.PubMedCrossRefGoogle Scholar
  5. 5.
    Herzig, S. and Neumann, J., Physiol. Rev., 2000, vol. 80, pp. 173–210.PubMedGoogle Scholar
  6. 6.
    Groth, R., Dunbar, R., and Mermelstein, P., Biochem. Biophys. Res. Commun., 2003, vol. 311, pp. 1159–1171.PubMedCrossRefGoogle Scholar
  7. 7.
    Sun, T., Wu, X., Xu, J., McNeil, B., Pang, Z., Yang, W., Bai, L., Qadri, S., Molkentin, J., Yue, D., and Wu, L.-G., J. Neurosci., 2010, vol. 30, pp. 11838–11847.PubMedCrossRefGoogle Scholar
  8. 8.
    Xie, C., Neuromolecular Med., 2004, vol. 6, pp. 53–64.PubMedCrossRefGoogle Scholar
  9. 9.
    Qian, W., Yin, X., Hu, W., Shi, J., Gu, J., Grundke-Iqbal, I., Iqbal, K., Gong, C., and Liu, F., J. Alzheimers Dis., 2011, vol. 23, pp. 617–627.PubMedGoogle Scholar
  10. 10.
    Sanderson, J. and Dell’Acqua, M., Neuroscientist, 2011, vol. 17, pp. 321–336.PubMedCrossRefGoogle Scholar
  11. 11.
    Flink, M. and Atchison, W., J. Pharmacol. Exp. Ther., 2003, vol. 305, pp. 646–652.PubMedCrossRefGoogle Scholar
  12. 12.
    Sagoo, J., Fruman, D., Wesselborg, S., Walsh, C., and Bierer, B., Biochem. J., 1996, vol. 320, pp. 879–884.PubMedGoogle Scholar
  13. 13.
    Schuhmann, K., Romanin, C., Baumgartner, W., and Groschner, K., J. Gen. Physiol., 1997, vol. 110, pp. 503–513.PubMedCrossRefGoogle Scholar
  14. 14.
    Oliveria, S., Dell’Acqua, M., and Sather, W., Neuron, 2007, vol. 55, pp. 261–275.PubMedCrossRefGoogle Scholar
  15. 15.
    Tandan, S., Wang, Y., Wang, T., Jiang, N., Hall, D., Hell, J., Luo, X., Rothermel, B., and Hill, J., Circ. Res., 2009, vol. 105, pp. 51–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Urbano, F., Depetris, R., and Uchitel, O., Pflugers Arc., 2001, vol. 441, pp. 824–831.CrossRefGoogle Scholar
  17. 17.
    Giovannini, F., Sher, E., Webster, R., Boot, J., and Lang, B., Br. J. Pharmacol., 2002, vol. 136, pp. 1135–1145.PubMedCrossRefGoogle Scholar
  18. 18.
    Perissinotti, P., Giugovaz, Tropper, B., and Uchitel, O., Eur. J. Neurosci., 2008, vol. 27, pp. 1333–1344.PubMedCrossRefGoogle Scholar
  19. 19.
    Gaydukov, A., Melnikova, S., and Balezina, O., Bull. Exp. Biol. Med., 2009, vol. 148, pp. 163–166.PubMedCrossRefGoogle Scholar
  20. 20.
    Atchison, W., J. Pharmacol. Exp. Ther., 1989, vol. 251, pp. 672–678.PubMedGoogle Scholar
  21. 21.
    Hunt, J., Silinsky, E., Hirsch, J., Ahn, D., and Solosona, C., Eur. J. Pharmacol., 1990, vol. 178, pp. 259–266.PubMedCrossRefGoogle Scholar
  22. 22.
    Bencherif, M., Eisenhour, C., Prince, R., Lippiello, P., and Lukas, R., J. Pharmacol. Exp. Ther., 1995, vol. 275, pp. 1418–1426.PubMedGoogle Scholar
  23. 23.
    Yamashita, T., Neurosci. Res., 2012, vol. 73, pp. 1–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Sim, A., Baldwin, M., Rostas, J., Holst, J., and Ludowyke, R., Biochem. J., 2003, vol. 373, pp. 641–659.PubMedCrossRefGoogle Scholar
  25. 25.
    Kumashiro, S., Lu, Y., Tomizawa, K., Matsushita, M., Wei, F., and Matsui, H., Neurosci. Res., 2005, vol. 51, pp. 435–443.PubMedCrossRefGoogle Scholar
  26. 26.
    Hardwick, J. and Parsons, R., J. Neurophysiol., 1996, vol. 76, pp. 3609–3616.PubMedGoogle Scholar
  27. 27.
    Etherington, S. and Everett, A., J. Physiol., 2004, vol. 559, pp. 507–517.PubMedCrossRefGoogle Scholar
  28. 28.
    Norris, C., Blalock, E., Chen, K., Porter, N., and Landfield, P., Neuroscience, 2002, vol. 110, pp. 213–225.PubMedCrossRefGoogle Scholar
  29. 29.
    Cameron, A., Steiner, J., Roskams, A., Ali, S., Ronnett, G., and Snyder, S., Cell, 1995, vol. 83, pp. 463–472.PubMedCrossRefGoogle Scholar
  30. 30.
    Ozawa, T., Perspect. Medicin. Chem., 2008, vol. 2, pp. 51–55.PubMedGoogle Scholar
  31. 31.
    Shin, D., Pan, Z., Bandyopadhyay, A., Bhat, M., Kim, D., and Ma, J., Biophys. J., 2002, vol. 83, pp. 2539–2549.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  • A. E. Gaydukov
    • 1
    • 2
    Email author
  • E. O. Tarasova
    • 1
  • O. P. Balezina
    • 1
  1. 1.Department of Human and Animals Physiology, Biological FacultyMoscow State UniversityMoscowRussia
  2. 2.MoscowRussia

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