Skip to main content
SpringerLink
Log in

β-Adrenergic modulation of calcium channels in frog ventricular heart cells

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Adrenergic modulation of calcium channels profoundly influences cardiac function1,2, and has served as a prime example of neurohormonal regulation of voltage-gated ion channels1–7. Channel modulation and increased Ca influx2,8,9 are mediated by elevation of intracellular cyclic AMP10–17 and protein phosphorylation18,19. The molecular mechanism of the augmented membrane Ca conductance has attracted considerable interest. An increase in the density of functional channels has often been proposed20–22, but there has previously been no direct evidence. Single-channel recordings show that isoprenaline or 8-bromocyclic AMP increase the proportion of time individual channels spend open by prolonging openings and shortening the closed periods between openings2,23–25. To look for an additional contribution of changes in the number of functional channels, we applied ensemble fluctuation analysis26 to whole-cell recordings27,28 of cardiac Ca channel activity. Here we present evidence that in frog ventricular heart cells β-adrenergic stimulation increases NF, the average number of functional Ca channels per cell. We also find that isoprenaline slows the time course of both activation and inactivation, and that the enhancement of peak current decreases gradually with greater membrane depolarization.

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. Tsien, R. W. & Siegelbaum, S. A. in Physiology of Membrane Disorders (eds Andreoli, T. E., Huffman, J. F. & Fanestil, D. D.) 517–538 (Plenum, New York, (1978).

    Book  Google Scholar 

  2. Reuter, H. A. Rev. Physiol. 41, 413–424 (1979).

    Article  CAS  Google Scholar 

  3. Kehoe, J. & Marty, A. A. Rev. Biophys. Bioengng 9, 437–465 (1980).

    Article  CAS  Google Scholar 

  4. Nicoll, R. A. Trends Neurosci. 5, 369–374 (1983).

    Article  Google Scholar 

  5. Reuter, H. Nature 301, 569–574 (1983).

    Article  ADS  CAS  Google Scholar 

  6. Tsien, R. W. A. Rev. Physiol. 45, 341–358 (1983).

    Article  CAS  Google Scholar 

  7. Siegelbaum, S. A. & Tsien, R. W. Trends Neurosci. 6, 307–313 (1983).

    Article  CAS  Google Scholar 

  8. Vassort, G. et al. Pflügers Arch. ges. Physiol. 309, 70–81 (1969).

    Article  CAS  Google Scholar 

  9. Brown, H. F., McNaughton, P. A., Noble, D. & Noble, S. J. Phil. Trans. R. Soc. B270, 527–537 (1975).

    Article  CAS  Google Scholar 

  10. Tsien, R. W., Giles, W. & Greengard, P. Nature new Biol. 240, 181–183 (1972).

    Article  CAS  Google Scholar 

  11. Meinertz, T., Nawrath, H. & Scholz, H. Naunyn-Schmiedebergs Archs Pharmak. 279, 327–338 (1973).

    Article  CAS  Google Scholar 

  12. Watanabe, A. M. & Besch, H. R. Circulation Res. 35, 316–324 (1974).

    Article  CAS  Google Scholar 

  13. Reuter, H. J. Physiol., Lond. 242, 429–451 (1974).

    Article  CAS  Google Scholar 

  14. Vogel, S. & Sperelakis, N. J. molec. cell. Cardiol. 13, 51–64 (1981).

    Article  CAS  Google Scholar 

  15. Trautwein, W., Taniguchi, J. & Noma, A. Pflügers Arch. ges. Physiol. 392, 307–314 (1982).

    Article  CAS  Google Scholar 

  16. Nargeot, J., Nerbonne, J. M., Engels, J. & Lester, H. A. Proc. natn. Acad. Sci. U.S.A. (in the press).

  17. Tsien, R. W. Adv. Cyclic Nucleotide Res. 8, 363–420 (1977).

    CAS  PubMed  Google Scholar 

  18. Osterrieder, W. et al. Nature 298, 576–578 (1977).

    Article  ADS  Google Scholar 

  19. Rinaldi, M. L., Capony, J.-P. & Demaille, J. G. J. molec. cell. Cardiol. 14, 279–289 (1982).

    Article  CAS  Google Scholar 

  20. Sperelakis, N. & Schneider, J. Am. J. Cardiol. 37, 1079–1085 (1976).

    Article  CAS  Google Scholar 

  21. Reuter, H. & Scholz, H. J. Physiol., Lond. 264, 49–62 (1977).

    Article  CAS  Google Scholar 

  22. Niedergerke, R. & Page, S. Proc. R. Soc. B197, 333–367 (1977).

    ADS  CAS  Google Scholar 

  23. Reuter, H., Stevens, C. F., Tsien, R. W. & Yellen, G. Nature 297, 501–504 (1982).

    Article  ADS  CAS  Google Scholar 

  24. Cachelin, A. B., de Peyer, J. E., Kokubun, S. & Reuter, H. Nature 304, 462–464 (1983).

    Article  ADS  CAS  Google Scholar 

  25. Reuter, H., Cachelin, A. B., de Peyer, J. E. & Kokubun, S. Cold Spring Harb. Symp. quant. Biol. 48 (in the press).

  26. Sigworth, F. J. J. Physiol., Lond. 307, 97–129 (1980).

    Article  CAS  Google Scholar 

  27. Hamill, O., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflügers Arch. ges. Physiol. 391, 85–100 (1981).

    Article  CAS  Google Scholar 

  28. Fenwick, E. M., Marty, A. & Neher, E. J. Physiol., Lond. 331, 599–635 (1982).

    Article  CAS  Google Scholar 

  29. Cranefield, P. F. & Gadsby, D. C. J. Physiol., Lond. 318, 34–35P (1981).

    Google Scholar 

  30. Lee, K. S. & Tsien, R. W. Nature 302, 790–794 (1983).

    Article  ADS  CAS  Google Scholar 

  31. Sigworth, F. J. J. Physiol., Lond. 307, 131–142 (1980).

    Article  CAS  Google Scholar 

  32. Noma, A., Kotake, H. & Irisawa, H. Pflügers Arch. ges. Physiol. 388, 1–9 (1980).

    Article  CAS  Google Scholar 

  33. Kass, R. A., Wiegers, S. E. J. Physiol., Lond. 322, 541–558 (1982).

    Article  CAS  Google Scholar 

  34. Hume, J. R. & Giles, W. J. gen. Physiol. 78, 19–42 (1981).

    Article  CAS  Google Scholar 

  35. Tarr, M., Trank, J. W. Experientia 32, 338–339 (1976).

    Article  CAS  Google Scholar 

  36. Harary, I., Hoover, F. & Farley, B. Meth. Enzym. 32, 740–745 (1974).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Physiology and Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Bruce P. Bean, Martha C. Nowycky & Richard W. Tsien

Authors
  1. Bruce P. Bean
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martha C. Nowycky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard W. Tsien
    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

Bean, B., Nowycky, M. & Tsien, R. β-Adrenergic modulation of calcium channels in frog ventricular heart cells. Nature 307, 371–375 (1984). https://doi.org/10.1038/307371a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/307371a0

  • Springer Nature Limited

This article is cited by

Search

Navigation