Skip to main content
SpringerLink
Log in

Zn2+ potentiates ATP-activated currents in rat sympathetic neurons

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The ATP-activated inward current (I ATP) in cultured rat superior cervical ganglion neurons and its modulation by extracellular Zn2+ were examined. ATP activated a non-specific cation conductance and caused a transient rise in intracellular Ca2+. The current response was specifically activated by ATP and was blocked by the P2-purinoceptor antagonist, suramin. Low concentrations of extracellular Zn2+ rapidly and reversibly potentiated both I ATP and the intracellular Ca2+ rise. The potentiation by 10 μM Zn2+ was dependent on the concentration of agonist; Zn2+ increased the sensitivity of activation without potentiating the maximum response. Higher concentrations of Zn2+ reduced and prolonged the current, consistent with open-channel block. We hypothesize that there exist two sites of action for Zn2+: a positively acting allosteric site that enhances current amplitude and a site, possibly within the pore, that blocks conductance through the channel.

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. Allen TGJ, Burnstock G (1990) The actions of adenosine 5′-triphosphate on guinea-pig intracardiac neurones in culture. Br J Pharmacol 100:269–276

    Google Scholar 

  2. Assaf SY Chung S (1984) Release of endogenous Zn2+ from brain tissue during activity. Nature 308:734–736

    Google Scholar 

  3. Bean BP (1990) ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. J Neurosci 10:1–10

    Google Scholar 

  4. Bean BP, Friel DD (1990) ATP-activated channels in excitable cells. In: Navahashi T (ed) Ion channels. Plenum, New York, pp 169–203

    Google Scholar 

  5. Bean BP, Williams CA, Ceelen PW (1990) ATP-activated channels in rat and bullfrog sensory neurons: current-voltage relation and single-channel behavior. J Neurosci 10:11–19

    Google Scholar 

  6. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24:509–581

    Google Scholar 

  7. Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440

    Google Scholar 

  8. Busselberg D, Michael D, Evans ML, Carpenter DO, Haas HL (1992) Zinc (Zn2+) blocks voltage gated calcium channels in cultured rat dorsal root ganglion cells. Brain Res 593:77–81

    Google Scholar 

  9. Celentano JJ, Gyenes M, Gibbs TT, Farb DH (1991) Negative modulation of the gamma-aminobutyric acid response by extracellular zinc. Mol Pharmacol 40:766–773

    Google Scholar 

  10. Clementi E, Scheer H, Raichman M, Meldolesi J (1992) ATP-induced Ca2+ influx is regulated via a pertussis toxin sensitive mechanism in a PC12 cell clone. Biochem Biophys Res Commun 188:1184–1190

    Google Scholar 

  11. Crawford IL, Connor JD (1972) Zinc in maturing rat brain: hippocampal concentration and localization. J Neurochem 19:1451–1458

    Google Scholar 

  12. Dunn PM, Blakeley AGH (1988) Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol 93:243–245

    Google Scholar 

  13. Dvergsten CL, Fosmire GJ, Ollerich DA, Sandstead HH (1983) Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. I. Impaired acquisition of granule cells. Brain Res 271:217–226

    Google Scholar 

  14. Edwards FA, Gibb AJ, Colquhoun D (1992) ATP receptor-mediated synaptic currents in the central nervous system. Nature 359:144–147

    Google Scholar 

  15. Evans RJ, Derkach V, Surprenant A (1992) ATP mediates fast synaptic transmission in mammalian neurons. Nature 357:503–505

    Google Scholar 

  16. Fieber LA, Adams DJ (1991) Adenosine triphosphate-evoked currents in cultured neurones dissociated from rat parasympathetic cardiac ganglia. J Physiol (Lond) 434:239–256

    Google Scholar 

  17. Friedman B, Price JL (1984) Fiber systems in the olfactory bulb and cortex: a study in adult and developing rats, using the Timm method with the light and electron microscope. J Comp Neurol 223:88–109

    Google Scholar 

  18. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450

    Google Scholar 

  19. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100

    Google Scholar 

  20. Hirano Y, Okajima F, Tomura H, Majid MA, Takeuchi T, Kondo Y (1991) Change of intracellular calcium of neural cells induced by extracellular ATP. FEBS Lett 284:235–237

    Google Scholar 

  21. Howell GA, Welch MG, Frederickson CJ (1984) Stimulation-induced uptake and release of zinc in hippocampal slices. Nature 308:736–738

    Google Scholar 

  22. Hoyle CHV (1992) Transmission: purines. In: Burnstock G, Hoyle CHV (eds) Autonomic neuroeffector mechanisms. Harwood, Reading, pp 367–407

    Google Scholar 

  23. Hurley LS, Shrader RE (1972) Congenital malformations of the nervous system in zinc-deficient rats. Int Rev Neurobiol [Suppl] 1:7–51

    Google Scholar 

  24. Itoh M, Ebadi M (1982) The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures. Neurochem Res 7:1287–1298

    Google Scholar 

  25. Jahr CE, Jessel TM (1983) ATP excites a subpopulation of rat dorsal horn neurones. Nature 304:730–733

    Google Scholar 

  26. Krishtal OA, Marchenko SM, Pidoplichko VI (1983) Receptor for ATP in the membrane of mammalian sensory neurones. Brain Res 41–45

  27. Legendre P, Westbrook GL (1991) Noncompetitive inhibition of gamma-aminobutyric acid channels by zinc. Mol Pharmacol 39:267–274

    Google Scholar 

  28. Li C, Peoples RW, Li Z, Weight FF (1992) Zinc potentiates ATP-activated inward current in rat nodose ganglion neurons. Soc Neurosci Abstr 18:1503

    Google Scholar 

  29. Magneson GR, Puvathingal JM, Ray WJ Jr (1987) The concentrations of free Mg2+ and free Zn2+ in equine blood plasma. J Biol Chem 262:11 140–11 148

    Google Scholar 

  30. Marrion NV, Smart TG, Brown DA (1987) Membrane currents in adult rat superior cervical ganglia in dissociated tissue culture. Neurosci Lett 77:55–60

    Google Scholar 

  31. Nakazawa K, Fujimori K, Takanaka A, Inoue K (1990) An ATP-activated conductance in pheochromocytoma cells and its suppression by extracellular calcium. J Physiol (Lond) 428:257–272

    Google Scholar 

  32. Peters S, Koh J, Choi DW (1987) Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. Science 236:589–593

    Google Scholar 

  33. Rassendren FA, Lory P, Pin JP, Nargeot J (1990) Zinc has opposite effects on NMDA and non-NMDA receptors expressed in Xenopus oocytes. Neuron 4:733–740

    Google Scholar 

  34. Robbins J, Trouslard J, Marsh SJ, Brown DA (1992) Kinetic and pharmacological properties of the m-current in rodent neuroblastoma X glioma hybrid cells. J Physiol (Lond) 451:159–185

    Google Scholar 

  35. Sim JA, Cherubini E (1990) Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro. Neuroscience 36:623–629

    Google Scholar 

  36. Smart TG (1992) A novel modulatory binding site for zinc on the GABA receptor complex in cultured rat neurones. J Physiol (Lond) 447:587–625

    Google Scholar 

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

    Google Scholar 

  38. Westbrook GL, Mayer ML (1987) Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 328:640–643

    Google Scholar 

  39. Wright DM (1984) Zinc: effect and interaction with other cations in the cortex of the rat. Brain Res 311:343–347

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK

    Robin Cloues, Susan Jones & David A. Brown

Authors
  1. Robin Cloues
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David A. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cloues, R., Jones, S. & Brown, D.A. Zn2+ potentiates ATP-activated currents in rat sympathetic neurons. Pflugers Arch. 424, 152–158 (1993). https://doi.org/10.1007/BF00374606

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00374606

Key words

Search

Navigation