Neurochemical Journal

, Volume 2, Issue 3, pp 175–182 | Cite as

Role of the cAMP cascade in the turnover of synaptic vesicles of the frog motor nerve terminal

  • A. M. Petrov
  • A. R. Giniatullin
  • A. L. Zefirov
Experimental Articles


In experiments with frog neuromuscular preparations we have shown with the use of electrophysiological (two-electrode voltage clamp) and optical (fluorescent exocytotic dye FM1-43) techniques that during high-frequency stimulation (20 imp/s, 3 min) the cyclic adenosine monophosphate (cAMP) system had a complex effect on the exo-endocytotic cycle of synaptic vesicles. The activation of cAMP-dependent enzymes (100 μM 8-Br-cAMP, 50 μM Bt2-cAMP) was accompanied by facilitation of exocytosis of the vesicles from a ready-to-release pool and enhancement of the endocytosis of synaptic vesicles. However, transport of the vesicles from the mobilization pool to the ready-to-release pool was disturbed and transmitter release was supported by the vesicles from the reserve pool. Blockage of adenylate cyclase (1 μM MDL) suppressed exocytosis of the vesicles from the ready-to-release pool, hindered replenishment of this pool with vesicles from the mobilization and reserve pools, and impaired endocytosis. Thus, stimulation of the cAMP pathway promotes vesicle recycling via a slow pathway and maintenance of transmitter release during high-frequency activity via vesicles from the reserve pool, whereas the background activity of adenylate cyclase is necessary for the effective development of all the key stages of the vesicular cycle.

Key words

exocytosis endocytosis recycling of synaptic vesicles vesicular pools cAMP end plate currents FM1-43 


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  1. 1.
    Heuser, J.E., Reese, T.S., Dennis, M.J., and Jan, L., J. Cell Biol., 1979, vol. 81, pp. 275–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Sudhof, T.C., Annu. Rev. Neurosci., 2004, vol. 27, pp.509–547.PubMedCrossRefGoogle Scholar
  3. 3.
    Zhai, R.G. and Bellen, H.J., J. Physiol., 2004, vol. 19, pp. 262–270.CrossRefGoogle Scholar
  4. 4.
    Gundelfinger, E.M., Kessels, M.M., and Qualmann, B., Nature Rev. Mol. Cell Biol., 2003, vol. 4, pp. 127–139.CrossRefGoogle Scholar
  5. 5.
    Betz, W.J. and Angelson, J.K., Annu. Rev. Physiol., 1998, vol. 60, pp. 347–363.PubMedCrossRefGoogle Scholar
  6. 6.
    Kavalali, E. T., Neuroscientist, 2006, vol. 12, no. 1, pp. 57–66.PubMedCrossRefGoogle Scholar
  7. 7.
    Micheva, K.D., Buchanana, J., Holz, R.W., and Smith, S.J., Nature Neurosci., 2003, vol. 6, no. 9, pp. 925–932.PubMedCrossRefGoogle Scholar
  8. 8.
    Rizzoli, S.O. and Betz, W.J., Nature Rev. Neurosci., 2005, vol. 6, pp. 57–69.CrossRefGoogle Scholar
  9. 9.
    Richards, D.A., Guatimosim, C., and Betz, W.J., Neuron, 2000, vol. 27, pp. 551–559.PubMedCrossRefGoogle Scholar
  10. 10.
    Rohrbough, J. and Broadie, K., Nature Rev. Neurosci., 2005, vol. 6, pp. 139–150.CrossRefGoogle Scholar
  11. 11.
    Wenk, M.R. and De Camilli, P., Proc. Nat. Acad. Sci., 2004, vol. 101, no. 6, pp. 8262–8269.PubMedCrossRefGoogle Scholar
  12. 12.
    Seino, S. and Shibasaki, T., Physiol. Rev., 2005, vol. 85, pp. 1303–1342.PubMedCrossRefGoogle Scholar
  13. 13.
    Verstreken, P., Ly, C., Venken, K.J.T., et al., Neuron, 2005, vol. 47, pp. 365–378.PubMedCrossRefGoogle Scholar
  14. 14.
    Zefirov, A.L., Grigor’ev, P.N., Petrov, A.M., et al., Tsitologiya, 2003, vol. 45, no. 12, pp. 1163–1171.Google Scholar
  15. 15.
    Zefirov A.L., Abdrakhmanov, M.M., Grigor’ev, P.N., and Petrov, A.M., Tsitologiya, 2006, vol. 48, no. 1, pp. 34–41.Google Scholar
  16. 16.
    Betz, W.J. and Bewick, G.S., J. Physiol. Lond., 1993, vol. 460, pp. 287–309.PubMedGoogle Scholar
  17. 17.
    Reid, B., Slater, C.R., and Bewick, G.S., J. Neurosci., 1999, vol. 19, no. 7, pp. 2511–2521.PubMedGoogle Scholar
  18. 18.
    Hepp, R., Cabaniols, J.P., and Roche, P.A., FEBS Lett., 2002, vol. 532, pp. 52–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Nagy, G., Reim, K., Matti, U., et al., Neuron, 2004, vol. 41, pp. 351–365.CrossRefGoogle Scholar
  20. 20.
    Evans, G.J. and Morgan, A., J. Biochem., 2002, vol. 364, pp. 343–347.CrossRefGoogle Scholar
  21. 21.
    Chheda, M.G., Ashery, U., Thakur, P., et al., Nat. Cell Biol., 2001, vol. 3, pp. 331–338.PubMedCrossRefGoogle Scholar
  22. 22.
    Barder, M.-F., Dousssau, F., Chasserot-Golaz, S., et al., Biochim. Biophys. Acta., 2004, vol. 1742. pp. 37–49.CrossRefGoogle Scholar
  23. 23.
    Wang, Y., Chen, Y., Chen, M., and Xu, W., Oncol. Reports, 2006, vol. 16. pp. 755–761.Google Scholar
  24. 24.
    Gaffield, M.A., Rizzoli, S.O., and Betz, W.J., Neuron, 2006, vol. 51, pp. 317–325.PubMedCrossRefGoogle Scholar
  25. 25.
    Kuromi, H. and Kidokoro, Y., Neuron, 2002, vol. 35, pp. 333–343.PubMedCrossRefGoogle Scholar
  26. 26.
    Jovanovic, J.N, Sihra, T.S., Narin, A.C., et al., J. Neurosci., 2001, vol. 21. pp. 7944–7953.PubMedGoogle Scholar
  27. 27.
    Richards, D.A, Rizzoli, S.O., and Betz, W.J., J. Physiol., 2004, vol. 557, no. 1, pp. 77–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Tasken, K. and Aandahl, E.M., Physiol. Rev., 2004, vol. 84, pp. 137–167.PubMedCrossRefGoogle Scholar

Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • A. M. Petrov
    • 1
  • A. R. Giniatullin
    • 1
  • A. L. Zefirov
    • 1
  1. 1.Kazan State UniversityKazan, TatarstanRussia

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