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Influence of purinergic modulators on eEPSCs in rat CA3 hippocampal neurons: Contribution of ionotropic ATP receptors

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Abstract

ATP is considered to impact on fast synaptic transmission in several regions of the CNS, including the CA1 and CA3 areas of the hippocampus. The existing paradigm suggests that ATP induces synaptic responses in CA3 pyramidal cells, and a fast ATP-mediated component is observed in cultured hippocampal slices mainly under conditions of a synchronous discharge from multiple presynaptic inputs. We confirmed the existence of a fast ATP-mediated component within electrically evoked EPSCs (eEPSCs) in CA3 neurons of acute slices of the rat hippocampus using a whole-cell patch-clamp recording mode. In approximately 50% of the examined cells, eEPSCs were not completely inhibited by co-applied glutamate receptor antagonists, NBQX (50 µM) and D-APV (25 µM). The residual current was sensitive to ionotropic P2X receptor antagonists, such as suramin (25 µM) and NF023 (2 µM). Known purinergic receptor modulators, ivermectin (10 µM) and PPADS (10 µM), practically did not affect EPSCs, whereas a nonhydrolyzable ATP analog, ATPγS (100 µM), slightly decreased the EPSC amplitude. Moreover, ATPγS (100 µM) at a holding potential of −70 mV generated a slow inward current in most recorded neurons, which was insensitive to glutamate receptor antagonists. This fact is indicative of the ionotropic P2X receptor activation.

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References

  1. G. Burnstock, “Purine and pyrimidine receptors,” Cell Mol. Life Sci., 64, 1471–1483 (2007).

    Article  PubMed  CAS  Google Scholar 

  2. B. P. Bean, C. A. Williams, and P. W. Ceelen, “ATP-activated channels in rat and bullfrog sensory neurons: current-voltage relation and single-channel behavior,” J. Neurosci., 10, 11–19 (1990).

    PubMed  CAS  Google Scholar 

  3. R. J. Evans and V. Derkach, “ATP mediates fast synaptic transmission in mammalian neurons,” Nature, 357, 503–505 (1992).

    Article  PubMed  CAS  Google Scholar 

  4. L. A. Fieber and D. J. Adams, “Adenosine triphosphate-evoked currents in cultured neurons dissociated from rat parasympathetic cardiac ganglia,” J. Physiol., 434, 239–256 (1991).

    PubMed  CAS  Google Scholar 

  5. O. A. Krishtal, S. M. Marchenko, and A. G. Obukhov, “Cationic channels activated by extracellular ATP in rat sensory neurons,” Neuroscience, 27, 995–1000 (1988).

    Article  PubMed  CAS  Google Scholar 

  6. A. Surprenant, G. Buell, and R. A. North, “P2x receptors bring new structure to ligand-gated ion channels,” Trends Neurosci., 18, 224–229 (1995).

    Article  PubMed  CAS  Google Scholar 

  7. F. A. Edwards, A. J. Gibb, and D. Colquhoun, “ATP receptor-mediated synaptic currents in the central nervous system,” Nature, 359, 144–147 (1992).

    Article  PubMed  CAS  Google Scholar 

  8. K. Nieber, W. Poelchen, and P. Illes, “Role of ATP in fast excitatory synaptic potentials in locus coeruleus neurones of the rat,” Br. J. Pharmacol., 122, 423–430 (1997).

    Article  PubMed  CAS  Google Scholar 

  9. S. Ueno, N. Harata, K. Inoue, and N. Akaike, “ATP-gated current in dissociated rat nucleus solitarii neurons,” J. Neurophysiol., 68, 778–785 (1992).

    PubMed  CAS  Google Scholar 

  10. M. F. Ireland, P. G. Noakes, and M. C. Bellingham, “P2x7-like receptor subunits enhance excitatory synaptic transmission at central synapses by presynaptic mechanisms,” Neuroscience, 128, 269–280 (2004).

    Article  PubMed  CAS  Google Scholar 

  11. S. Boehm, “ATP stimulates sympathetic transmitter release via presynaptic P2x purinoceptors,” J. Neurosci., 19, 737–746 (1999).

    PubMed  CAS  Google Scholar 

  12. J. W. Deitmer, J. Brockhaus, and D. Casel, “Modulation of synaptic activity in Purkinje neurons by ATP,” Cerebellum, 5, 49–54 (2006).

    Article  PubMed  CAS  Google Scholar 

  13. Y. Pankratov, U. Lalo, O. Krishtal, and A. Verkhratsky, “P2x receptor-mediated excitatory synaptic currents in somatosensory cortex,” Mol. Cell Neurosci., 24, 842–849 (2003).

    Article  PubMed  CAS  Google Scholar 

  14. Y. Pankratov, U. Lalo, E. Castro, et al., “ATP receptor-mediated component of the excitatory synaptic transmission in the hippocampus,” Prog. Brain Res., 120, 237–249 (1999).

    Article  PubMed  CAS  Google Scholar 

  15. Y. V. Pankratov, U. V. Lalo, and O. A. Krishtal, “Role for P2X receptors in long-term potentiation,” J. Neurosci., 22, No. 19, 8363–8369 (2002).

    PubMed  CAS  Google Scholar 

  16. Y. Pankratov, U. Lalo, A. Verkhratsky, and R. A. North, “Quantal release of ATP in mouse cortex,” J. Gen. Physiol., 129, 257–265 (2007).

    Article  PubMed  CAS  Google Scholar 

  17. M. Mori, C. Heuss, B. H. Gahwiler, and U. Gerber, “Fast synaptic transmission mediated by P2x receptors in CA3 pyramidal cells of rat hippocampal slice cultures,” J. Physiol., 535, 115–123 (2001).

    Article  PubMed  CAS  Google Scholar 

  18. M. E. Rubio and F. Soto, “Distinct localization of P2x receptors at excitatory postsynaptic specializations,” J. Neurosci., 21, 641–653 (2001).

    PubMed  CAS  Google Scholar 

  19. B. S. Khakh, W. B. Smith, C. S. Chiu, et al., “Activation-dependent changes in receptor distribution and dendritic morphology in hippocampal neurons expressing P2x2-green fluorescent protein receptors,” Proc. Natl. Acad. Sci. USA, 98, 5288–5293 (2001).

    Article  PubMed  CAS  Google Scholar 

  20. W. Norenberg and P. Illes, “Neuronal P2x receptors: localisation and functional properties,” Naunyn-Schmiedeberg’s Arch. Pharmacol., 362, 324–339 (2000).

    Article  CAS  Google Scholar 

  21. S. J. Robertson, S. J. Ennion, R. J. Evans, and F. A. Edwards, “Synaptic P2x receptors,” Curr. Opin. Neurobiol., 11, 378–386 (2001).

    Article  PubMed  CAS  Google Scholar 

  22. J. A. Sim, S. Chaumont, J. Jo, et al., “Altered hippocampal synaptic potentiation in P2x4 knock-out mice,” J. Neurosci., 26, 9006–9009 (2006).

    Article  PubMed  CAS  Google Scholar 

  23. A. De Simoni, C. B. Griesinger, and F. A. Edwards, “Development of rat CA1 neurons in acute versus organotypic slices: role of experience in synaptic morphology and activity,” J. Physiol., 550, Part 1, 135–147 (2003).

    Article  PubMed  CAS  Google Scholar 

  24. B. S. Khakh, D. Gittermann, D. A. Cockayne, and A. Jones, “ATP modulation of excitatory synapses onto interneurons,” J. Neurosci., 23, 7426–7437 (2003).

    PubMed  CAS  Google Scholar 

  25. M. Ikeda, “Characterization of functional P2X(1) receptors in mouse megakaryocytes,” Thromb. Res., 119, 343–353 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. Y. H. Jo and R. Schlichter, “Synaptic corelease of ATP and GABA in cultured spinal neurons,” Nat. Neurosci., 2, 241–245 (1999).

    Article  PubMed  CAS  Google Scholar 

  27. C. Kennedy, G. J. Mclaren, T. D. Westfall, and P. Sneddon, “ATP as a co-transmitter with noradrenaline in sympathetic nerves — function and fate,” CIBA Found. Symp., 198, 223–235 (1996).

    PubMed  CAS  Google Scholar 

  28. I. von Kugelgen, C. Allgaier, A. Schobert, and K. Starke, “Co-release of noradrenaline and ATP from cultured sympathetic neurons,” Neuroscience, 61, 199–202 (1994).

    Article  Google Scholar 

  29. A. Wieraszko, G. Goldsmith, and T. N. Seyfried, “Stimulation-dependent release of adenosine triphosphate from hippocampal slices,” Brain Res., 485, 244–250 (1989).

    Article  PubMed  CAS  Google Scholar 

  30. Y. Pankratov, U. Lalo, A. Verkhratsky, and R. A. North, “Vesicular release of ATP at central synapses,” Pflügers Arch., 452, 589–597 (2006).

    Article  PubMed  CAS  Google Scholar 

  31. G. R. Gordon, D. V. Baimoukhametova, S. A. Hewitt, et al., “Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy,” Nat. Neurosci., 8, 1078–1086 (2005).

    Article  PubMed  CAS  Google Scholar 

  32. F. Soto, G. Lambrecht, P. Nickel, et al., “Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2x receptors,” Neuropharmacology, 38, 141–149 (1999).

    Article  PubMed  CAS  Google Scholar 

  33. H. Shiokawa, T. Nakatsuka, H. Furue, et al., “Direct excitation of deep dorsal horn neurons in the rat spinal cord by the activation of postsynaptic P2x receptors,” J. Physiol., 573, 753–763 (2006).

    Article  PubMed  CAS  Google Scholar 

  34. G. Wollmann, C. Cuna-Goycolea, and A. N. Van Den Pol, “Direct excitation of hypocretin/orexin cells by extracellular ATP at P2x receptors,” J. Neurophysiol., 94, 2195–2206 (2005).

    Article  PubMed  CAS  Google Scholar 

  35. T. M. Egan, D. S. Samways, and Z. Li, “Biophysics of P2X receptors,” Pflügers Arch., 452, 501–512 (2006).

    Article  PubMed  CAS  Google Scholar 

  36. P. M. Dunn and A. G. Blakeley, “Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens,” Br. J. Pharmacol., 93, 243–245 (1988).

    PubMed  CAS  Google Scholar 

  37. H. Uneyama, C. Uneyama, S. Ebihara, and N. Akaike, “Suramin and reactive blue 2 are antagonists for a newly identified purinoceptor on rat megakaryocyte,” Br. J. Pharmacol., 111, 245–249 (1994).

    PubMed  CAS  Google Scholar 

  38. A. Priel and S. D. Silberberg, “Mechanism of ivermectin facilitation of human P2x4 receptor channels,” J. Gen. Physiol., 123, 281–293 (2004).

    Article  PubMed  CAS  Google Scholar 

  39. B. S. Khakh, W. R. Proctor, T. V. Dunwiddie, et al., “Allosteric control of gating and kinetics at P2x(4) receptor channels,” J. Neurosci., 19, 7289–7299 (1999).

    PubMed  CAS  Google Scholar 

  40. E. Toulme, F. Soto, M. Garret, and E. Boue-Grabot, “Functional properties of internalization-deficient P2x4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin,” Mol. Pharmacol., 69, 576–587 (2006).

    Article  PubMed  CAS  Google Scholar 

  41. Y. Wang, J. Mackes, S. Chan, et al., “Impaired long-term depression in P2x3 deficient mice is not associated with a spatial learning deficit,” J. Neurochem., 99, 1425–1434 (2006).

    Article  PubMed  CAS  Google Scholar 

  42. R. A. Cunha, E. S. Vizi, J. A. Ribeiro, and A. M. Sebastiao, “Preferential release of ATP and its extracellular catabolism as a source of adenosine upon high-but not low-frequency stimulation of rat hippocampal slices,” J. Neurochem., 67, 2180–2187 (1996).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to E. Kondratskaya.

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Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 21–29, January–February, 2008.

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Kondratskaya, E., Nonaka, K. & Akaike, N. Influence of purinergic modulators on eEPSCs in rat CA3 hippocampal neurons: Contribution of ionotropic ATP receptors. Neurophysiology 40, 17–25 (2008). https://doi.org/10.1007/s11062-008-9011-x

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  • DOI: https://doi.org/10.1007/s11062-008-9011-x

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