Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell

Nature volume 323, pages 333–335 (1986)Cite this article

Abstract

Hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) produces two prospective intracellular messengers: inositol-l,4,5-trisphosphate (InsP3), which releases Ca2+" from intracellular stores1 ; and diacylglycerol (DG), which activates protein kinase C2. Here we show how the formation of these two substances triggered by one external messenger, bradykinin, leads to the appearance of two different sequential membrane conductance changes in the neurone-like NG108-15 (ref. 3) neuroblastoma-glioma hybrid cell line. In these cells bradykinin rapidly hydrolyses PtdIns(4,5)P2 to InsP3 and DG4,5, raises intracellular Ca2+ (refs 4, 6–8) and hyperpolarizes then depolarizes the cell membrane4,8,9. By voltage-clamp recording we show that the hyperpolarization results from the activation pharmacologically-identifiable species of Ca2+-dependent K+ current. This is also activated by intracellular injections of Ca2+ or InsP3 so may be attributed to the formation and action of InsP3. The subsequent depolarization results primarily from the inhibition of a different, voltage-dependent K+ current, the M-current10 that is also inhibited by DG activators. Hence we describe for the first time a dual, time-dependent role for these two intracellular messengers in the control of neuronal signalling by a peptide.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).

    Article  ADS  CAS  Google Scholar 

  2. Nishizuka, Y. Nature 308, 693–698 (1984).

    Article  ADS  CAS  Google Scholar 

  3. Nirenberg, M. et al. Science 222, 794–799 (1983).

    Article  ADS  CAS  Google Scholar 

  4. Yano, K., Higashida, H., Inoue, R. & Nozawa, Y. J biol Chem 259, 1201–1207 (1984).

    Google Scholar 

  5. Yano, K., Higashida, H., Hattori, H. & Nozawa, Y. FEBS Lett 181, 403–406 (1985).

    Article  CAS  Google Scholar 

  6. Reiser, G. & Hamprecht, B. Pflüg Arch ges Physiol 405, 260–264 (1985).

    Article  CAS  Google Scholar 

  7. Osugi, T., Uchida, S., Imaizumi, T. & Yoshida, H. Brain Res (in the press).

  8. Higashida, H., Streaty, R. A., Klee, W & Nirenberg, M. Proc. natn. Acad. Sci. U.S.A. 83, 942–946 (1986).

    Article  ADS  CAS  Google Scholar 

  9. Reiser, G. & Hamprecht, B. Brain Res 239, 191–199 (1982).

    Article  CAS  Google Scholar 

  10. Brown, D. A. & Adams, P. R. Nature 283, 673–676 (1980).

    Article  ADS  CAS  Google Scholar 

  11. Fishman, M. C. & Spector, I. Proc. natn. Acad. Sci. U.S.A. 78, 5245–5249 (1981).

    Article  ADS  CAS  Google Scholar 

  12. Hermann, A. & Hartung, K. Pflüg. Arch. ges. Physiol. 393, 248–261 (1982).

    Article  CAS  Google Scholar 

  13. Adams, P. R., Constanti, A., Clark, R. B. & Brown, D. A. Nature 296, 746–749 (1982).

    Article  ADS  CAS  Google Scholar 

  14. Marty, A. Trends Neurosci 6, 262–265 (1983).

    Article  CAS  Google Scholar 

  15. Lazdunski, M. Cell Calcium 4, 421–428 (1983).

    Article  CAS  Google Scholar 

  16. Jenkinson, D. H., Haylett, D. G. & Cook, N. S. Cell Calcium 4, 429–437 (1983).

    Article  CAS  Google Scholar 

  17. Hugues, M., Romey, G., Duval, D., Vincent, J. P. & Lazdunski, M. Proc. natn. Acad. Sci. U.S.A. 79, 1308–1312 (1982).

    Article  ADS  CAS  Google Scholar 

  18. Nohmi, M. & Kuba, K. Brain Res. 301, 146–148 (1984).

    Article  CAS  Google Scholar 

  19. Pennefather, P., Lancaster, B., Adams, P. R. & Nicoll, R. A. Proc. natn. Acad. Sci. U.S.A. 82, 3040–3044 (1985).

    Article  ADS  CAS  Google Scholar 

  20. Kawai, T. & Watanake, M. Br. J. Pharmac. 87, 225–232 (1986).

    Article  CAS  Google Scholar 

  21. Yellen, G. Nature 296, 357–359 (1982).

    Article  ADS  CAS  Google Scholar 

  22. Adams, P. R., Brown, D. A. & Constanti, A. J. Physiol., Lond. 332, 223–262 (1982).

    Article  CAS  Google Scholar 

  23. Adams, P. R. & Brown, D. A. Biophys. J. 49, 215a (1986).

    Google Scholar 

  24. Baraban, J. M., Snyder, S. H. & Alger, B. E. Proc. natn. Acad. Sci. U.S.A. 82, 2538–2542 (1985).

    Article  ADS  CAS  Google Scholar 

  25. Malenka, R. C., Madison, D. V., Andrade, R. & Nicoll, R. A. J. Neurosci. 6, 475–480 (1986).

    Article  CAS  Google Scholar 

  26. Madison, D. V., Malenka, R. C. & Nicoll, R. A. Nature 321, 695–697 (1986).

    Article  ADS  CAS  Google Scholar 

  27. Rane, S. C. & Dunlap, K. Proc. natn. Acad. Sci., U.S.A. 83, 184–188 (1986).

    Article  ADS  CAS  Google Scholar 

  28. Oran, Y., Dascal, N., Nadler, E. & Lupu, M. Nature 313, 141–143 (1985).

    Article  ADS  Google Scholar 

  29. Dascal, N., Lotan, I., Gillo, B., Lester, H. A. Lass, Y . Proc. natn. Acad. Sci. U.S.A. 82, 6001–6005 (1985).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Author notes

  1. David A. Brown

    Present address: MRC Neuropharmacology Research Group, Department of Pharmacology, University of London School of Pharmacy, London, WC1 1AX, UK

Authors and Affiliations

  1. Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute,

    Haruhiro Higashida

  2. Fogarty International Center and Laboratory of Cell Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Haruhiro Higashida

Authors
  1. Haruhiro Higashida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. 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

Higashida, H., Brown, D. Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. Nature 323, 333–335 (1986). https://doi.org/10.1038/323333a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/323333a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing