Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel (original) (raw)

Nature volume 340, pages 230–233 (1989)Cite this article

Abstract

IN cardiac muscle, where Ca2+ influx across the sarcolemma is essential for contraction, the dihydropyridine (DHP)-sensitive L-type calcium channel1 represents the major entry pathway of extracellular Ca2+. We have previously elucidated the primary structure of the rabbit skeletal muscle DHP receptor by cloning and sequencing the complementary DNA2. An expression plasmid carrying this cDNA, microinjected into cultured skeletal muscle cells from mice with muscular dysgenesis, has been shown to restore both excitation-contraction coupling and slow calcium current missing from these cells, so that a dual role for the DHP receptor in skeletal muscle transverse tubules is suggested3. We report here the complete amino-acid sequence of the rabbit cardiac DHP receptor, deduced from the cDNA sequence. We also show that messenger RNA derived from the cardiac DHP receptor cDNA is sufficient to direct the formation of a functional DHP-sensitive calcium channel in Xenopus oocytes. Furthermore, higher calcium-channel activity is observed when mRNA specific for the polypeptide of relative molecular mass ∼140,000 (α2-subunit)4–6 associated with the skeletal muscle DHP receptor is co-injected.

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References

  1. Bean, B. P. A. Rev. Physiol. 51, 367–384 (1989).
    Article CAS Google Scholar
  2. Tanabe, T. et al. Nature 328, 313–318 (1987).
    Article CAS ADS Google Scholar
  3. Tanabe, T., Beam, K. G., Powell, J. A. & Numa, S. Nature 336, 134–139 (1988).
    Article CAS ADS Google Scholar
  4. Catterall, W. A. Science 242, 50–61 (1988).
    Article CAS ADS Google Scholar
  5. Campbell, K. P., Leung, A. T. & Sharp, A. H. Trends Neurosci. 11, 425–430 (1988).
    Article CAS Google Scholar
  6. Hosey, M. M. & Lazdunski, M. J. Membrane Biol. 104, 81–105 (1988).
    Article CAS Google Scholar
  7. Noda, M. et al. Nature 312, 121–127 (1984).
    Article CAS ADS Google Scholar
  8. Noda, M. et al. Nature 320, 188–192 (1986).
    Article CAS ADS Google Scholar
  9. Kayano, T., Noda, M., Flockerzi, V., Takahashi, H. & Numa, S. FEBS Lett. 228, 187–194 (1988).
    Article CAS Google Scholar
  10. Salkoff, L. et al. Science 237, 744–749 (1987).
    Article CAS ADS Google Scholar
  11. Hubbard, S. C. & Ivatt, R. J. A. Rev. Biochem. 50, 555–583 (1981).
    Article CAS Google Scholar
  12. Krebs, E. G. & Beavo, J. A. A. Rev. Biochem. 48, 923–959 (1979).
    Article CAS Google Scholar
  13. Dascal, N., Snutch, T. P., Lübbert, H., Davidson, N. & Lester, H. A. Science 231, 1147–1150 (1986).
    Article CAS ADS Google Scholar
  14. Noda, M. et al. Nature 322, 826–828 (1986).
    Article CAS ADS Google Scholar
  15. Stühmer, W., Methfessel, C., Sakmann, B., Noda, M. & Numa, S. Eur. Biophys. J. 14, 131–138 (1987).
    Article Google Scholar
  16. Suzuki, H. et al. FEBS Lett. 228, 195–200 (1988).
    Article CAS Google Scholar
  17. Auld, V. J. et al. Neuron 1, 449–461 (1988).
    Article CAS Google Scholar
  18. Timpe, L. C. et al. Nature 331, 143–145 (1988).
    Article CAS ADS Google Scholar
  19. Stühmer, W. et al. FEBS Lett. 242, 199–206 (1988).
    Article Google Scholar
  20. Noguchi, S., Mishina, M., Kawamura, M. & Numa, S. FEBS Lett. 225, 27–32 (1987).
    Article CAS Google Scholar
  21. Leberer, E. et al. J. biol. Chem. 264, 3484–3493 (1989).
    CAS PubMed Google Scholar
  22. Noda, M. et al. Nature 295, 202–206 (1982).
    Article CAS ADS Google Scholar
  23. Henikoff, S. Meth. Enzym. 155, 156–165 (1987).
    Article CAS Google Scholar
  24. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
    Article CAS ADS Google Scholar
  25. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).
    Article CAS Google Scholar
  26. Mishina, M. et al. Nature 321, 406–411 (1986).
    Article CAS ADS Google Scholar
  27. Mishina, M. et al. Nature 307, 604–608 (1984).
    Article CAS ADS Google Scholar
  28. Fukuda, K. et al. Nature 327, 623–625 (1987).
    Article CAS ADS Google Scholar
  29. Ellis, S. B. et al. Science 241, 1661–1664 (1988).
    Article CAS ADS Google Scholar
  30. Methfessel, C. et al. Pflügers Arch. ges. Physiol. 407, 577–588 (1986).
    Article CAS Google Scholar

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Author notes

  1. Shuh Narumiya
    Present address: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, 606, Japan

Authors and Affiliations

  1. Departments of Medical Chemistry and Molecular Genetics, Kyoto University Faculty of Medicine, Kyoto, 606, Japan
    Atsushi Mikami, Keiji Imoto, Tsutomu Tanabe, Tetsuhiro Niidome, Yasuo Mori, Hiroshi Takeshima, Shuh Narumiya & Shosaku Numa

Authors

  1. Atsushi Mikami
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  2. Keiji Imoto
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  3. Tsutomu Tanabe
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  4. Tetsuhiro Niidome
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  5. Yasuo Mori
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  6. Hiroshi Takeshima
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  7. Shuh Narumiya
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  8. Shosaku Numa
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Mikami, A., Imoto, K., Tanabe, T. et al. Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.Nature 340, 230–233 (1989). https://doi.org/10.1038/340230a0

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