Skip to main content
SpringerLink
Log in

Purinergic modulation of synaptic signalling at the neuromuscular junction

  • Invited Review
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Purines have physiologically important functions throughout the nervous system. In both the central (CNS) and peripheral nervous systems (PNS), purines in the form of adenosine triphosphate and adenosine can play a number of roles in neuronal activation and inhibition. In addition, purines are known to be important for glial cell signaling in both the CNS and PNS. In the PNS, the neuromuscular junction (NMJ) is an excellent model for studying simple synaptic interactions. It is well suited to investigations of neuron-glia interactions because synaptic properties are well defined and perisynaptic Schwann cells (PSCs), glial cells at the NMJ, dynamically interact with the pre- and postsynaptic elements. At the NMJ, purines are critical for presynaptic modulation but also for neuron-glia interactions. Purines signal to PSCs through metabotropic and ionotropic receptors and activation of these receptors can have both modulatory and activating functions. This review will discuss recent developments in our understanding of purinergic modulation of the NMJ with an emphasis on the involvement of purines in neuron-glia interactions at this synapse.

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

Fig. 1

Similar content being viewed by others

References

  1. Ansselin AD, Davey DF, Allen DG (1997) Extracellular ATP increases intracellular calcium in cultured adult Schwann cells. Neuroscience 76:947–955

    Article  PubMed  CAS  Google Scholar 

  2. Auld DS, Robitaille R (2003) Perisynaptic Schwann cells at the neuromuscular junction: nerve- and activity-dependent contributions to synaptic efficacy, plasticity, and reinnervation. Neuroscientist 9:144–157

    Article  PubMed  Google Scholar 

  3. Baxter RL, Vega-Riveroll LJ, Deuchars J, Parson SH (2005) A2A adenosine receptors are located on presynaptic motor nerve terminals in the mouse. Synapse 57:229–234

    Article  PubMed  CAS  Google Scholar 

  4. Bourque MJ, Robitaille R (1998) Endogenous peptidergic modulation of perisynaptic Schwann cells at the frog neuromuscular junction. J Physiol 512:197–209

    Article  PubMed  CAS  Google Scholar 

  5. Castonguay A, Robitaille R (2001) Differential regulation of transmitter release by presynaptic and glial Ca2+ internal stores at the neuromuscular synapse. J Neurosci 21:1911–1922

    PubMed  CAS  Google Scholar 

  6. Choi RC, Man ML, Ling KK, Ip NY, Simon J, Barnard EA, Tsim KW (2001) Expression of the P2Y1 nucleotide receptor in chick muscle: its functional role in the regulation of acetylcholinesterase and acetylcholine receptor. J Neurosci 21:9224–9234

    PubMed  CAS  Google Scholar 

  7. Choi RC, Siow NL, Cheng AW, Ling KK, Tung EK, Simon J, Barnard EA, Tsim KW (2003) ATP acts via P2Y1 receptors to stimulate acetylcholinesterase and acetylcholine receptor expression: transduction and transcription control. J Neurosci 23:4445–4456

    PubMed  CAS  Google Scholar 

  8. Collet C, Strube C, Csernoch L, Mallouk N, Ojeda C, Allard B, Jacquemond V (2002) Effects of extracellular ATP on freshly isolated mouse skeletal muscle cells during pre-natal and post-natal development. Pflugers Arch 443:771–778

    Article  PubMed  CAS  Google Scholar 

  9. Colomar A, Amedee T (2001) ATP stimulation of P2X(7) receptors activates three different ionic conductances on cultured mouse Schwann cells. Eur J Neurosci 14:927–936

    Article  PubMed  CAS  Google Scholar 

  10. Correia-de-Sa P, Timoteo MA, Ribeiro JA (1996) Presynaptic A1 inhibitory/A2A facilitatory adenosine receptor activation balance depends on motor nerve stimulation paradigm at the rat hemidiaphragm. J Neurophysiol 76:3910–3919

    PubMed  CAS  Google Scholar 

  11. Cunha RA (2001) Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int 38:107–125

    Article  PubMed  CAS  Google Scholar 

  12. Descarries LM, Cai S, Robitaille R, Josephson EM, Morest DK (1998) Localization and characterization of nitric oxide synthase at the frog neuromuscular junction. J Neurocytol 27:829–840

    Article  PubMed  CAS  Google Scholar 

  13. Fu WM, Poo MM (1991) ATP potentiates spontaneous transmitter release at developing neuromuscular synapses. Neuron 6:837–843

    Article  PubMed  CAS  Google Scholar 

  14. Galkin AV, Giniatullin RA, Mukhtarov MR, Svandova I, Grishin SN, Vyskocil F (2001) ATP but not adenosine inhibits nonquantal acetylcholine release at the mouse neuromuscular junction. Eur J Neurosci 13:2047–2053

    Article  PubMed  CAS  Google Scholar 

  15. Georgiou J, Robitaille R, Trimble WS, Charlton MP (1994) Synaptic regulation of glial protein expression in vivo. Neuron 12:443–455

    Article  PubMed  CAS  Google Scholar 

  16. Georgiou J, Robitaille R, Charlton MP (1999) Muscarinic control of cytoskeleton in perisynaptic glia. J Neurosci 19:3836–3846

    PubMed  CAS  Google Scholar 

  17. Giniatullin RA, Sokolova EM (1998) ATP and adenosine inhibit transmitter release at the frog neuromuscular junction through distinct presynaptic receptors. Br J Pharmacol 124:839–844

    Article  PubMed  CAS  Google Scholar 

  18. Giniatullin AR, Grishin SN, Sharifullina ER, Petrov AM, Zefirov AL, Giniatullin RA (2005) Reactive oxygen species contribute to the presynaptic action of extracellular ATP at the frog neuromuscular junction. J Physiol 565:229–242

    Article  PubMed  CAS  Google Scholar 

  19. Grafe P, Mayer C, Takigawa T, Kamleiter M, Sanchez-Brandelik R (1999) Confocal calcium imaging reveals an ionotropic P2 nucleotide receptor in the paranodal membrane of rat Schwann cells. J Physiol 515(Pt 2):377–383

    Article  PubMed  CAS  Google Scholar 

  20. Grishin S, Shakirzyanova A, Giniatullin A, Afzalov R, Giniatullin R (2005) Mechanisms of ATP action on motor nerve terminals at the frog neuromuscular junction. Eur J Neurosci 21:1271–1279

    Article  PubMed  CAS  Google Scholar 

  21. Hamilton BR, Smith DO (1991) Autoreceptor-mediated purinergic and cholinergic inhibition of motor nerve terminal calcium currents in the rat. J Physiol 432:327–341

    PubMed  CAS  Google Scholar 

  22. Huang SM, Kitamura A, Akita T, Narita K, Kuba K (2002) Adenosine depresses a Ca(2+)-independent step in transmitter exocytosis at frog motor nerve terminals. Eur J Neurosci 15:1291–1298

    Article  PubMed  Google Scholar 

  23. Jahromi BS, Robitaille R, Charlton MP (1992) Transmitter release increases intracellular calcium in perisynaptic Schwann cells in situ. Neuron 8:1069–1077

    Article  PubMed  CAS  Google Scholar 

  24. Liu GJ, Werry EL, Bennett MR (2005) Secretion of ATP from Schwann cells in response to uridine triphosphate. Eur J Neurosci 21:151–160

    Article  PubMed  Google Scholar 

  25. Lyons SA, Morell P, McCarthy KD (1994) Schwann cells exhibit P2Y purinergic receptors that regulate intracellular calcium and are up-regulated by cyclic AMP analogues. J Neurochem 63:552–560

    Article  PubMed  CAS  Google Scholar 

  26. Lyons SA, Morell P, McCarthy KD (1995) Schwann cell ATP-mediated calcium increases in vitro and in situ are dependent on contact with neurons. Glia 13:27–38

    Article  PubMed  CAS  Google Scholar 

  27. Moores TS, Hasdemir B, Vega-Riveroll L, Deuchars J, Parson SH (2005) Properties of presynaptic P2X7-like receptors at the neuromuscular junction. Brain Res 1034:40–50

    Article  PubMed  CAS  Google Scholar 

  28. Oliveira L, Timoteo MA, Correia-de-Sa P (2002) Modulation by adenosine of both muscarinic M1-facilitation and M2-inhibition of [3H]-acetylcholine release from the rat motor nerve terminals. Eur J Neurosci 15:1728–1736

    Article  PubMed  Google Scholar 

  29. Oliveira L, Timoteo MA, Correia-de-Sa P (2004) Tetanic depression is overcome by tonic adenosine A(2A) receptor facilitation of L-type Ca(2+) influx into rat motor nerve terminals. J Physiol 560:157–168

    Article  PubMed  CAS  Google Scholar 

  30. Redman RS, Silinsky EM (1994) ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings. J Physiol 477:117–127

    PubMed  CAS  Google Scholar 

  31. Robitaille R (1995) Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. J Neurosci 15:7121–7131

    PubMed  CAS  Google Scholar 

  32. Robitaille R (1998) Modulation of synaptic efficacy and synaptic depression by glial cells at the frog neuromuscular junction. Neuron 21:847–855

    Article  PubMed  CAS  Google Scholar 

  33. Robitaille R, Jahromi BS, Charlton MP (1997) Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction. J Physiol 504:337–347

    Article  PubMed  CAS  Google Scholar 

  34. Robitaille R, Thomas S, Charlton MP (1999) Effects of adenosine on Ca2+ entry in the nerve terminal of the frog neuromuscular junction. Can J Physiol Pharmacol 77:707–714

    Article  PubMed  CAS  Google Scholar 

  35. Rochon D, Rousse I, Robitaille R (2001) Synapse–glia interactions at the mammalian neuromuscular junction. J Neurosci 21:3819–3829

    PubMed  CAS  Google Scholar 

  36. Santos DA, Salgado AI, Cunha RA (2003) ATP is released from nerve terminals and from activated muscle fibres on stimulation of the rat phrenic nerve. Neurosci Lett 338:225–228

    Article  PubMed  CAS  Google Scholar 

  37. Silinsky EM (1975) On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol 247:145–162

    PubMed  CAS  Google Scholar 

  38. Silinsky EM (2004) Adenosine decreases both presynaptic calcium currents and neurotransmitter release at the mouse neuromuscular junction. J Physiol 558:389–401

    Article  PubMed  CAS  Google Scholar 

  39. Silinsky EM (2005) Modulation of calcium currents is eliminated after cleavage of a strategic component of the mammalian secretory apparatus. J Physiol 566:681–678

    Article  CAS  Google Scholar 

  40. Smith DO (1991) Sources of adenosine released during neuromuscular transmission in the rat. J Physiol 432:343–354

    PubMed  CAS  Google Scholar 

  41. Son YJ, Thompson WJ (1995) Schwann cell processes guide regeneration of peripheral axons. Neuron 14:125–132

    Article  PubMed  CAS  Google Scholar 

  42. Stevens B, Fields RD (2000) Response of Schwann cells to action potentials in development. Science 287:2267–2271

    Article  PubMed  CAS  Google Scholar 

  43. Stevens B, Ishibashi T, Chen JF, Fields RD (2004) Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells. Neuron Glia Biol 1:23–34

    Article  PubMed  Google Scholar 

  44. Thomas S, Robitaille R (2001) Differential frequency-dependent regulation of transmitter release by endogenous nitric oxide at the amphibian neuromuscular synapse. J Neurosci 21:1087–1095

    PubMed  CAS  Google Scholar 

  45. Todd KJ, Robitaille R (2006) Neuron–glia interactions at the neuromuscular synapse. In: Chadwick DJ, Goode J (eds) Symposium on purinergic signalling in neuron–glia interactions, Novartis Foundation, London, 7–9 June 2006, no. 276

    Google Scholar 

  46. Tung EK, Choi RC, Siow NL, Jiang JX, Ling KK, Simon J, Barnard EA, Tsim KW (2004) P2Y2 receptor activation regulates the expression of acetylcholinesterase and acetylcholine receptor genes at vertebrate neuromuscular junctions. Mol Pharmacol 66:794–806

    Article  PubMed  CAS  Google Scholar 

  47. Zimmermann H, Braun N, Kegel B, Heine P (1998) New insights into molecular structure and function of ectonucleotidases in the nervous system. Neurochem Int 32:421–425

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Claude Gauthier for help with the figure preparation. This work was supported by grants to RR from the Canadian Institutes for Health Research, from the National Science and Engineering Research Council (NSERC), and by a group grant from Fonds de la recherché en Santé du Québec. KJT was supported by a NSERC studentship.

Author information

Authors and Affiliations

  1. Département de Physiologie and Centre de Recherche en Sciences Neurologiques, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, Québec H3C 3J7, Canada

    Keith J. Todd & Richard Robitaille

Authors
  1. Keith J. Todd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Robitaille
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard Robitaille.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Todd, K.J., Robitaille, R. Purinergic modulation of synaptic signalling at the neuromuscular junction. Pflugers Arch - Eur J Physiol 452, 608–614 (2006). https://doi.org/10.1007/s00424-006-0068-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-006-0068-3

Keywords

Search

Navigation