Skip to main content

Thank you for visiting 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.

Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase


THE ryanodine receptor protein of skeletal muscle sarcoplasmic reticulum (SR) membranes is a calcium ion channel which allows movement of calcium from the SR lumen into the cytoplasm during muscle activation1–5. Gating of this channel is modulated by a number of physiologically important substances including calcium. Interestingly, calcium has both activating and inactivating effects which are concentration- and tissue-specific. In skeletal muscle, calcium-dependent inactivation of calcium release occurs at concentrations reached physiologically, suggesting that calcium may modulate the release process by a negative feedback mechanism6–9. To determine the cellular mechanism responsible for calcium-dependent inactivation, we have investigated the ability of protein phosphorylation to affect single channel gating behaviour using the patch clamp technique. Here we demonstrate that the ryanodine receptor protein/calcium release channel of skeletal muscle SR is inactivated under conditions permissive for protein phosphorylation. This inactivation is reversed by the application of phosphatase and prevented by a peptide inhibitor specific for calcium/cal-modulin-dependent protein kinase II. The results provide evidence for an endogenous protein kinase which is closely associated with the ryanodine receptor protein and regulates channel gating.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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


  1. Imagawa, T., Smith, J. S., Coronado, R. & Campbell, K. P. J. biol. Chem. 262, 16636–16643 (1987).

    CAS  PubMed  Google Scholar 

  2. Hymel, L., Inui, M., Fleischer, S. & Schindler, H. Proc. natn. Acad. Sci. U.S.A. 85, 441–445 (1988).

    Article  ADS  CAS  Google Scholar 

  3. Lai, F. A., Erickson, H. P., Rousseau, E., Liu, Q.-Y. & Meissner, G. Nature 331, 315–319 (1988).

    Article  ADS  CAS  Google Scholar 

  4. Catterall, W. A. Cell 64, 871–874 (1991).

    Article  CAS  Google Scholar 

  5. Smith, J. S. et al. J. gen. Physiol. 92, 1–26 (1988).

    Article  ADS  CAS  Google Scholar 

  6. Baylor, S. M., Chandler, W. K. & Marshall, M. W. J. Physiol. 344, 625–666 (1983).

    Article  CAS  Google Scholar 

  7. Schneider, M. F. & Simon, B. J. Physiol. 405, 727–745 (1988).

    Article  Google Scholar 

  8. Simon, B. J., Klein, M. G. & Schneider, M. F. J. gen. Physiol. 97, 437–471 (1991).

    Article  CAS  Google Scholar 

  9. Kwok, W.-M. & Best, P. M. Pflügers Arch. 419, 166–176 (1991).

    Article  CAS  Google Scholar 

  10. Stein, P. & Palade, P. Biophys. J. 54, 357–363 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Hals, G. D., Stein, P. G. & Palade, P. J. gen. Physiol. 93, 385–410 (1989).

    Article  CAS  Google Scholar 

  12. Morii, H., Takisawa, H. & Yamamoto, T. J. Biochem. 102, 263–271 (1987).

    Article  CAS  Google Scholar 

  13. Lüttgau, H. C. & Oetliker, H. J. Physiol., Lond. 194, 51–74 (1968).

    Article  Google Scholar 

  14. Campbell, K. P. & MacLennan, D. H. J. biol. Chem. 257, 1238–1246 (1982).

    CAS  PubMed  Google Scholar 

  15. Tuana, S. T. & MacLennan, D. H. FEBS Lett. 235, 219–223 (1988).

    Article  CAS  Google Scholar 

  16. Chu, A., Sumbilla, C., Inesi, G., Jay, S. D. & Campbell, K. P. Biochemistry 29, 5899–5905 (1990).

    Article  CAS  Google Scholar 

  17. Malinow, R., Schulman, H. & Tsien, R. W. Science 245, 862–865 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Wagner, J. A. et al. Nature 349, 793–796 (1991).

    Article  ADS  CAS  Google Scholar 

  19. Chung, S., Reinhart, P. H., Martin, B. L., Brautigan, D. & Levitan, I. B. Science 253, 560–562 (1991).

    Article  ADS  CAS  Google Scholar 

  20. Takeshima, H. et al. Nature 339, 439–445 (1989).

    Article  ADS  CAS  Google Scholar 

  21. Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42–52 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Witcher, D. R., Kovacs, R. J., Schulman, H., Cefali, D. C. & Jones, L. R. J. biol. Chem. 17, 11144–11152 (1991).

    Google Scholar 

  23. Kim, D. H. & Ikemoto, N. J. biol. Chem. 261, 11674–11679 (1986).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, J., Best, P. Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase. Nature 359, 739–741 (1992).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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