Normalization of current kinetics by interaction between the α1and β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel (original) (raw)

Nature volume 352, pages 527–530 (1991)Cite this article

Abstract

PURIFICATION of skeletal muscle dihydropyridine binding sites has enabled protein complexes to be isolated from which Ca2+ currents have been reconstituted. Complementary DNAs encoding the five subunits of the dihydropyridine receptor, α1, β, γ, α2 and δ (ref. 1), have been cloned2–6 and it is now recognized that α2 and δ are derived from a common precursor7,8. The α1, subunit can itself produce Ca2+ currents, as was demonstrated using mouse L cells lacking α2δ (refs 9,10), β (ref. 10) and γ (our unpublished results). In L cells, stable expression of skeletal muscle α1 alone was sufficient to generate voltage-sensitive, high-threshold L-type Ca2+ channel currents which were dihydropyridine-sensitive and blocked by Cd2+, but the activation kinetics were about 100 times slower than expected for skeletal muscle Ca2+ channel currents. This could have been due to the cell type in which α 1 , was being expressed or to the lack of a regulatory component particularly one of the subunits that copurifies with α1. We show here that coexpression of skeletal muscle β with skeletal muscle α1, generates cell lines expressing Ca2+ channel currents with normal activation kinetics as evidence for the participation of the dihydropyridine-receptor β subunits in the generation of skeletal muscle Ca2+ channel currents.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Catterall, W. A. Science 242, 50–61 (1988).
    Article ADS CAS Google Scholar
  2. Tanabe, T. et al. Nature 328, 313–318 (1987).
    Article ADS CAS Google Scholar
  3. Ellis, S. B. et al. Science 241, 1661–1664 (1988).
    Article ADS CAS Google Scholar
  4. Ruth, P. et al. Science 245, 1115–1118 (1989).
    Article ADS CAS Google Scholar
  5. Jay, S. D. et al. Science 248, 490–492 (1990).
    Article ADS CAS Google Scholar
  6. Bosse, E. et al. FEBS Lett. 267, 153–156 (1990).
    Article CAS Google Scholar
  7. DeJongh, K. S., Warner, C. & Catterall, W. A. J. blol. Chem. 265, 14738–14741 (1990).
    CAS Google Scholar
  8. Jay, S. D. et al. J. biol. Chem. 266, 3287–3293 (1991).
    CAS PubMed Google Scholar
  9. Perez-Reyes, E. et al. Nature 340, 233–236 (1989).
    Article ADS CAS Google Scholar
  10. Kim, H. S. et al. J. biol. Chem. 265, 11858–11863 (1990).
    CAS PubMed Google Scholar
  11. Nukada, T., Mishina, M. & Numa, S. FEBS Lett. 211, 5–9 (1987).
    Article CAS Google Scholar
  12. Wong, G. G. et al. Science 228, 810–815 (1985).
    Article ADS CAS Google Scholar
  13. Liao, C.-F. et al. J. biol. Chem. 264, 7328–7337 (1989).
    CAS PubMed Google Scholar
  14. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pfluegers Arch. ges. Physiol. 391, 85–100 (1981).
    Article CAS Google Scholar
  15. Lacerda, A. E. & Brown, A. M. J. gen. Physiol. 93, 1243–1273 (1989).
    Article CAS Google Scholar
  16. Cognard, C., Traore, F., Potreau, D. & Raymond, G. Pfluegers Arch. ges. Physiol. 407, 677–638 (1986).
    Article CAS Google Scholar
  17. Cognard, C., Romey, G., Galizzi, J.-P., Fosset, M. & Lazdunski, M. Proc. natn. Acad. Sci. U.S.A. 83, 1518–1522 (1986).
    Article ADS CAS Google Scholar
  18. Brown, A. M., Tsuda, Y. & Wilson, D. L. J. Physiol. 344, 549–583 (1983).
    Article CAS Google Scholar
  19. Schwartz, L. M., McCleskey, E. W. & Aimers, W. Nature 314, 747–750 (1985).
    Article ADS CAS Google Scholar
  20. Perez-Reyes, E., Wei, X., Castellano, A. & Birnbaumer, L. J. biol. Chem. 265, 20430–20436 (1990).
    CAS PubMed Google Scholar
  21. Mikami, A. et al. Nature 340, 230–233 (1989).
    Article ADS CAS Google Scholar

Download references

Author information

Author notes

  1. Peter Ruth & Franz Hofmann
    Present address: Institute of Pharmacology, Technical University of Munich, D-8000, Munich, Germany

Authors and Affiliations

  1. Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas, 77030, USA
    Antonio E. Lacerda, Edward Perez-Reyes, Lutz Birnbaumer & Arthur M. Brown
  2. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA
    Haeyoung S. Kim & Lutz Birnbaumer
  3. Department of Division of Neuroscience, Baylor College of Medicine, Houston, Texas, 77030, USA
    Lutz Birnbaumer
  4. Institute of Physiological Chemistry, Faculty of Medicine, University of Saarland, D-6650, Homburg/Saar, Saarland, Germany
    Peter Ruth, Veit Flockerzi & Franz Hofmann

Authors

  1. Antonio E. Lacerda
    You can also search for this author inPubMed Google Scholar
  2. Haeyoung S. Kim
    You can also search for this author inPubMed Google Scholar
  3. Peter Ruth
    You can also search for this author inPubMed Google Scholar
  4. Edward Perez-Reyes
    You can also search for this author inPubMed Google Scholar
  5. Veit Flockerzi
    You can also search for this author inPubMed Google Scholar
  6. Franz Hofmann
    You can also search for this author inPubMed Google Scholar
  7. Lutz Birnbaumer
    You can also search for this author inPubMed Google Scholar
  8. Arthur M. Brown
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Lacerda, A., Kim, H., Ruth, P. et al. Normalization of current kinetics by interaction between the α1and β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel.Nature 352, 527–530 (1991). https://doi.org/10.1038/352527a0

Download citation