Skip to main content
SpringerLink
Log in

The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

  • Articles
  • Published:
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The changes in spontaneous and evoked neurotransmitter release caused by agonists and antagonists of the A1and A2A-subtypes of adenosine receptors combined with inhibition of some enzymes and voltage-dependent calcium channels of L-type were studied in mouse diaphragm motor synapses using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs). Simultaneous activation of presynaptic A1 and A2A receptors by endogenous adenosine during short-term rhythmic activity of motor synapses was shown for the first time. Activation of receptors A1 prevails and is followed by downregulation of the ACh release due to inhibition of intracellular cascade, which involves protein kinase A (PKA) and L-type voltage-dependent calcium channels. Activation of receptors A2A with their agonist CGS-21680 caused upregulation of the ACh secretion due to enhancement of PKA activity followed by activation of L-type voltage-dependent calcium channels. The mechanism of the evoked release potentiation, when A1 receptors are blocked or the activity of A2A receptors prevails over that of A1 receptors, involves calcium release from ryanodine-sensitive intracellular calcium stores coupled with PKA and activation of L-type voltage-dependent calcium channels. It was found that protein phosphatase calcineurin participates in downregulation of the L-type voltage-dependent calcium channels irrespective of the A1 receptors. It was shown for the first time that disinhibition of L-type voltage-dependent calcium channels caused by the calcineurin inhibition requires participation of the activity of A2A receptors and PKA. In conclusion, reciprocal interactions between presynaptic receptors A1 and A2A and their effect on the ACh release were shown in motor synapses. These interactions are mediated by the following cascade: PKA → L-type voltage-dependent calcium channels → ryanodine receptors of calcium stores. Final effect on the neurotransmitter release depends on conditions of coactivation of these receptors and interplay of enzymes and L-type voltage-dependent calcium channels within synaptic terminals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Baxter R.L., Vega-Riveroll L.J., Deuchars J., Parson S.H. 2005. A2A adenosine receptors are located on presynaptic motor nerve terminals in the mouse. Synapse. 57 (4), 229–234.

    Article  PubMed  CAS  Google Scholar 

  2. Garcia N., Priego M., Obis T., Santafe M.M., Tomás M., Besalduch N., Lanuza M.A., Tomás J. 2013. Adenosine A and AAreceptor-mediated modulation of acetylcholine release in the mice neuromuscular junction. Eur. J. Neurosci. 38 (2), 2229–2241.

    Article  PubMed  Google Scholar 

  3. Correia-de-Sá P., Sebastião A.M., Ribeiro J.A. 1991. Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve ending of the rat. Br. J. Pharmacol. 103 (2), 1614–1620.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Correia-de-Sá P., Timóteo M.A., Ribeiro J.A. 1996. Presynaptic A1 inhibitory/A2A facilitatory adenosine receptor activation balance depends on motor nerve stimulation paradigm at the rat hemidiaphragm. J. Neurophysiol. 76 (6), 3910–3919.

    PubMed  Google Scholar 

  5. Oliveira L., Timóteo M.A., Correia-de-Sá P. 2004. Tetanic depression is overcome by tonic adenosine A(2A) receptor facilitation of L-type Ca2+ influx into rat motor nerve terminals. J. Physiol. 560 (Pt 1), 157–168.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Oliveira L., Correia-de-Sá P. 2005. Protein kinase A and CaV1 (L-type) channels are common targets to facilitatory adenosine A2A and muscarinic M1 receptors on rat motoneurons. Neurosignals. 14 (5), 262–272.

    Article  PubMed  CAS  Google Scholar 

  7. Urbano F.J., Depetris R.S., Uchitel O.D. 2001. Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals. Pflügers Arch. 441 (6), 824–831.

    Article  PubMed  CAS  Google Scholar 

  8. Pagani R., Song M., McEnery M., Qin N., Tsien R.W., Toro L., Stefani E., Uchitel O.D. 2004. Differential expression of α1and β-subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse. Neuroscience. 123 (1), 75–85.

    Article  PubMed  CAS  Google Scholar 

  9. Atchison W.D. 1989. Dihydropyridine-sensitive and -insensitive components of acetylcholine release from rat motor nerve terminals. J. Pharmacol. Exp. Ther. 251 (2), 672–678.

    PubMed  CAS  Google Scholar 

  10. Flink M.T., Atchison W.D. 2003. Iberiotoxin-induced block of Ca2+-activated K+ channels induces dihydropyridine sensitivity of ACh release from mammalian motor nerve terminals. J. Pharmacol. Exp. Ther. 305 (2), 646–652.

    Article  PubMed  CAS  Google Scholar 

  11. Gaydukov A.E., Tarasova E.O., Balezina O.P. 2013. Calcium-dependent phosphatase calcineurin downregulates evoked neurotransmitter release in neuromuscular junctions of mice. Neurochem. J. 7 (1), 29–33.

    Article  CAS  Google Scholar 

  12. Urbano F.J., Uchitel O.D. 1999. L-type calcium channels unmasked by cell-permeant Ca2+ buffer at mouse motor nerve terminals. Pflügers Arch. 437 (4), 523–528.

    Article  PubMed  CAS  Google Scholar 

  13. Gaydukov A.E., Marchenkova A.A., Balezina O.P. 2012. Facilitation of neurotransmitter release in mouse motor synapses in different modes of protein kinase C activation. Bull. Exp. Biol. Med. 153 (4), 415–418.

    Article  PubMed  CAS  Google Scholar 

  14. McLachlan E.M., Martin A.R. 1981. Non-linear summation of end-plate potentials in the frog and mouse. J. Physiol. 311, 307–324.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Fredholm B.B., Chen J.F., Cunha R.A., Svenningsson P., Vaugeois J.M. 2005. Adenosine and brain function. Int. Rev. Neurobiol. 63, 191–270.

    Article  PubMed  CAS  Google Scholar 

  16. Gaydukov A.E., Melnikova S.N., Balezina O.P. 2009. Facilitation of acetylcholine secretion in mouse motor synapses caused by calcium release from depots upon activation of L-type calcium channels. Bull. Exp. Biol. Med. 148 (2), 163–166.

    Article  PubMed  CAS  Google Scholar 

  17. Perissinotti P.P., Uchitel O.D. 2010. Adenosine drives recycled vesicles to a slow-release pool at the mouse neuromuscular junction. Eur. J. Neurosci. 32 (6), 985–996.

    Article  PubMed  Google Scholar 

  18. Schiffmann S.N., Fisone G., Moresco R., Cunha R.A., Ferré S. 2007. Adenosine A2A receptors and basal ganglia physiology. Prog. Neurobiol. 83 (5), 277–292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Sperlágh B., Vizi E.S. 2011. The role of extracellular adenosine in chemical neurotransmission in the hippocampus and basal ganglia: Pharmacological and clinical aspects. Curr. Top. Med. Chem. 11 (8), 1034–1046.

  20. Correia-de-Sá P., Timóteo M.A., Ribeiro J.A. 2000. Influence of stimulation on Ca2+ recruitment triggering [3H]acetylcholine release from the rat motor-nerve endings. Eur. J. Pharmacol. 406 (3), 355–362.

    Article  PubMed  Google Scholar 

  21. Oliveira L., Timóteo M.A., Correia-de-Sá P. 2009. Negative crosstalk between M1 and M2 muscarinic autoreceptors involves endogenous adenosine activating A1 receptors at the rat motor endplate. Neurosci. Lett. 459 (3), 127–131.

    Article  PubMed  CAS  Google Scholar 

  22. Tomás J., Santafé M.M., Garcia N., Lanuza M.A., Tomás M., Besalduch N., Obis T., Priego M., Hurtado E. 2014. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse. J. Neurosci. Res. 92 (5), 543–554.

    Article  PubMed  CAS  Google Scholar 

  23. Searl T.J., Silinsky E.M. 2012. Evidence for constitutively-active adenosine receptors at mammalian motor nerve endings. Eur. J. Pharmacol. 685 (1–3), 38–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Cunha R.A., Correia-de-Sá P., Sebastião A.M., Ribeiro J.A. 1996. Preferential activation of excitatory adenosine receptors at rat hippocampal and neuromuscular synapses by adenosine formed from released adenine nucleotides. Br. J. Pharmacol. 119 (2), 253–260.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Cunha R.A. 2008. Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity. Neurochem. Int. 52 (1–2), 65–72.

    Article  PubMed  CAS  Google Scholar 

  26. Hernández-González O., Hernández-Flores., Prieto G.A., Pérez-Burgos A., Arias-García M.A., Galarraga E., Bargas J. 2014. Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A2A receptors in striatal projection neurons. Purinergic Signal. 10 (2), 269–281.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Keef K.D., Hume J.R., Zhong J. 2001. Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases. Am. J. Physiol. Cell. Physiol. 281 (6), 1743–1756.

    Google Scholar 

  28. Calin-Jageman I., Lee A. 2008. CaV1 L-type Ca2+ channel signaling complexes in neurons. J. Neurochem. 105 (3), 573–583.

    Article  PubMed  CAS  Google Scholar 

  29. Navedo M.F., Santana L.F. 2013. CaV1.2 sparklets in heart and vascular smooth muscle. J. Mol. Cell. Cardiol. 58, 67–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Kim S., Yun H.M., Baik J.H., Chung K.C., Nah S.Y., Rhim H. 2007. Functional interaction of neuronal CaV1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus. J. Biol. Chem. 282 (45), 32877–32889.

    Article  PubMed  CAS  Google Scholar 

  31. Kubota M., Narita K., Murayama T., Suzuki S., Soga S., Usukura J., Ogawa Y., Kuba K. 2005. Type-3 ryanodine receptor involved in Ca2+-induced Ca2+ release and transmitter exocytosis at frog motor nerve terminals. Cell Calcium. 38 (6), 557–567.

    Article  PubMed  CAS  Google Scholar 

  32. Soga-Sakakibara S., Kubota M., Suzuki S., Akita T., Narita K., Kuba K. 2010. Calcium dependence of the priming, activation and inactivation of ryanodine receptors in frog motor nerve terminals. Eur. J. Neurosci. 32 (6), 948–962.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biology Department, Moscow Lomonosov State University, Leninskie Gory 1, build. 12, Moscow, 119234, Russia

    E. O. Tarasova, A. S. Miteva, A. E. Gaidukov & O. P. Balezina

Authors
  1. E. O. Tarasova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. Miteva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. E. Gaidukov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. P. Balezina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. O. Tarasova.

Additional information

Original Russian Text © E.O. Tarasova, A.S. Miteva, A.E. Gaidukov, O.P. Balezina, 2015, published in Biologicheskie Membrany, 2015, Vol. 32, No. 5–6, pp. 409–420.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tarasova, E.O., Miteva, A.S., Gaidukov, A.E. et al. The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses. Biochem. Moscow Suppl. Ser. A 9, 318–328 (2015). https://doi.org/10.1134/S1990747815050141

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990747815050141

Keywords

Search

Navigation