Molecular Properties of Voltage-Sensitive Calcium Channels

  • William A. Catterall
  • Michael J. Seagar
  • Masami Takahashi
  • Kazuo Nunoki
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 255)


Voltage sensitive calcium channels participate in action potential generation in electrically excitable cells and constitute an essential link between transient changes in membrane potential and a variety of cellular responses including secretion of neurotransmitters and hormones, initiation of contraction in cardiac and smooth muscle, and activation of second messenger responses in many cell types. Electrophysiological measurements have established the existence of multiple classes of calcium channels.1–4 Although work on many cell systems has contributed to current understanding of calcium channel function, the molecular properties of the channel have been investigated most thoroughly in skeletal muscle which has a particularly high density of calcium channels. This chapter will therefore focus primarily on skeletal muscle calcium channels.


Calcium Channel Transverse Tubule Voltage Sensitive Calcium Channel Dihydropyridine Calcium Channel Antagonist Calcium Channel Subunit 
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  1. 1.
    S. Hagiwara and L. Byerly, Calcium channel, Ann. Rev. Neurosci. 4:69 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    C. M. Armstrong and D. R. Matteson, Two distinct populations of calcium channels in a clonal line of pituitary cells, Science 227:65 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    E. Carbone and H. D. Lux, A low voltage-activated fully inactivating calcium channel in vertebrate sensory neurones, Nature 310:501 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    M.C. Nowycky, A. P. Fox, and R. W. Tsien, Three types of neuronal calcium channel with different calcium agonist sensitivity, Nature 316:440 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    J. Sanchez and E. Stefani, Inward calcium current in twitch muscle fibers of the frog, J. Physiol. (Lond.) 283:197 (1978).Google Scholar
  6. 6.
    W. Aimers, E. McCleskey, and P. Palade, in “Calcium in Biological Systems” R. P. Rubin, G. B. Weiss, J. W. Putney, Jr. eds., Plenum Press, New York, London, pp. 321–330 (1985).CrossRefGoogle Scholar
  7. 7.
    G. Cota and E. Stefani, A fast-activated inward calcium current in twitch muscle fibres of the frog (Rana montezume), J. Physiol. 370:151 (1986).PubMedGoogle Scholar
  8. 8.
    C. Cognard, M. Lazdunski, and G. Romey, Different types of Ca2+ channels in mammalian skeletal muscle cells in culture, Proc. Natl. Acad. Sci. USA 83:517 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    H. Glossmann, D. R. Ferry, and C. B. Boschek, Purification of the putative calcium channel from skeletal muscle with the aid of [3H]-nimodipine binding, Naunyn-Schmiedeberg’s Arch. Pharmacol. 323:1 (1983).CrossRefGoogle Scholar
  10. 10.
    M. Fosset, E. Jaimovich, E. Delpont, and M. Lazdunski, [3H] nitrendipine receptors in skeletal muscle. Properties and preferential localization in transverse tubules, J. Biol. Chem. 258:6086 (1983).PubMedGoogle Scholar
  11. 11.
    H. Glossmann, R. Ferry, A. Goll, J. Striessnig, and M. Schober, Calcium channels: Basic properties as revealed by radioligand binding studies, J. Cardio. Pharmacol. 7:520(1985).CrossRefGoogle Scholar
  12. 12.
    J. Galizzi, M. Borsotto, J. Barhanin, M. Fosset, and M. Lazdunski, Characterization and photoaffinity labeling of receptor sites for the Ca2+ channel inhibitors d-cis-diltiazem, (+)-bepridil, desmethoxyverapamil and (+)PN200-110 in skeletal muscle transverse tubule membranes, J. Biol. Chem. 261:1393 (1986).PubMedGoogle Scholar
  13. 13.
    D. Ferry, M. Rombusch, A. Goll, and H. Glossmann, Photoaffinity labelling of Ca2+ channels with [3H]azidopine, FEBS Lett. 169:112 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    J. Striessnig, H.-G. Knaus, M. Grabner, K. Moosburger, W. Seitz, H. Lietz, and H. Glossmann, Photoaffinity labelling of the phenylalkylamine receptor of the skeletal muscle transverse tubule calcium channel, FEBS Lett. 212:247 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    B. M. Curtis and W. A. Catterall, Solubilization of the calcium antagonist receptor from rat brain, J. Biol. Chem. 258:7280 (1983).PubMedGoogle Scholar
  16. 16.
    B. M. Curtis and W. A. Catterall, Purification of the calcium antagonist receptor of the voltage-sensitive calcium channel from skeletal muscle transverse tubules, Biochemistry 23:2113 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    M. Takahashi, M. Seagar, J. Jones, B.F.X. Reber, and W. A. Catterall, Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle, Proc. Natl. Acad. Sci. USA 84:5478 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Leung, T. Imagawa, and K. Campbell, Structural characterization of the 1,4 dihydropyridine receptor of the voltage-dependent Ca2+ channel from rabbit skeletal muscle, J. Biol. Chem. 262:7943 (1987).PubMedGoogle Scholar
  19. 19.
    A. H. Sharp, T. Imagawa, A. T. Leung, and K. P. Campbell, Identification and characterization of the dihydropyridine binding subunit of the skeletal muscle dihydropyridine receptor, J. Biol. Chem. 262:12309 (1987).PubMedGoogle Scholar
  20. 20.
    M. E. Morton and S. C. Froehner, Monoclonal antibody identifies a 200-kDa subunit of the dihydropyridine-sensitive calcium channel, J. Biol. Chem. 262:11904(1987).PubMedGoogle Scholar
  21. 21.
    P. L. Vaghy, J. Streissnig, K. Miwa, H.-G. Knaus, K. Itagaki, E. McKenna, H. Glossmann, and A. Schwartz, Identification of a novel 1,4-dihydropyridine-and phenylalkylamine-binding polypeptide in calcium channel preparations, J. Biol. Chem 262:14337 (1987).PubMedGoogle Scholar
  22. 22.
    W. A. Catterall, Molecular properties of voltage-sensitive sodium channels, Ann. Rev. Biochem. 55:953 (1986).PubMedCrossRefGoogle Scholar
  23. 23.
    A. Goldin, T. Smith, H. Lubbert, A. Dowsett, J. Marshall, V. Auld, W. Downey, L. C. Fritz, H. A. Lester, R. Dunn, W. A. Catterall, and N. Davidson, Messenger RNA coding for only the a subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes, Proc. Natl. Acad. Sci. USA 83:7503 (1986).PubMedCrossRefGoogle Scholar
  24. 24.
    M. Noda, T. Ikeda, T. Suzuki, H. Takeshima, Takahashi M., M. Kuno, and S. Numa, Expression of functional sodium channels from cloned cDNA, Nature 32:826 (1986).CrossRefGoogle Scholar
  25. 25.
    J. Barhanin, T. Coppola, A. Schmid, M. Borsotto, and M. Lazdunski, The calcium channel antagonists receptor form rabbit skeletal muscle. Reconstitution after purification and subunit characterization, Eur. J. Biochem. 164:525 (1987).PubMedCrossRefGoogle Scholar
  26. 26.
    B. M. Curtis and W. A. Catterall, Reconstitution of the voltage-sensitive calcium channel purified from skeletal muscle transverse tubules, Biochemistry 25:3077 (1986).PubMedCrossRefGoogle Scholar
  27. 27.
    V. Flockerzi, H.-J. Oeken, F. Hofmann, D. Pelzer, A. Cavalie, and W. Trautwein, Purified dihydropyridine binding site from skeletal muscle T-tubules in a functional calcium channel, Nature (Lond.) 323:66 (1986).CrossRefGoogle Scholar
  28. 28.
    J. Striessnig, A. Goll, K. Moosburger, and H. Glossmann, Purified calcium channels have three allosterically coupled drug receptors, FEBS Lett. 197:204 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    M. Schramm, G. Thomas, R. Towart, and G. Franckowiak, Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels, Nature 303:535 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    H. Reuter, Properties of two inward membrane currents in the heart. Ann. Rev. Physiol. 41:413 (1974).CrossRefGoogle Scholar
  31. 31.
    R. Tsien, B. Bean, P. Hess, J. Lansman, B. Nilius, and M. Nowycky, Mechanisms of calcium channel modulation by ß-adrenergic agents and dihydropyridine calcium agonists, J. Mol. Cell Cardiol. 18:691 (1986).PubMedCrossRefGoogle Scholar
  32. 32.
    G. Brum, V. Flockerzi, F. Hofmann, W. Osterrieder, and W. Trautwein, Injection of catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes, Pflugers Archiv. 398:147 (1983).PubMedCrossRefGoogle Scholar
  33. 33.
    J. Arreola, J. Calvo, M. C. Garcia, and J. A. Sanchez, Modulation of calcium channels of twitch skeletal muscle of the frog by adrenaline and cyclic adenosine monophosphate fibres, J. Physiol. (Lond.) 393:307 (1987).PubMedGoogle Scholar
  34. 34.
    B. M. Curtis and W. A. Catterall, Phosphorylation of the calcium antagonist receptor of the voltage-sensitive calcium channel by cAMP-dependent protein kinase, Proc. Natl. Acad. Sci. USA 82:2528(1985).PubMedCrossRefGoogle Scholar
  35. 35.
    T. Tanabe, H. Takeshima, A. Mikami, V. Flockerzi, H. Takahashi, K. Kanagawa, M. Kojima, H. Matsuo, T. Hirose, S. Numa, Primary structure of dihydropyridine binding calcium channel from rabbit skeletal muscle, Nature 328:313 (1987).PubMedCrossRefGoogle Scholar
  36. 36.
    M. Noda, T. Ikeda, T. Kayano, H. Suzuki, H. Takeshima, M. Kurasaki, H. Takahashi, and S. Numa, Existence of distinct sodium channel messenger RNAs in rat brain, Nature 320:188 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • William A. Catterall
    • 1
  • Michael J. Seagar
    • 1
  • Masami Takahashi
    • 1
  • Kazuo Nunoki
    • 1
  1. 1.Department of Pharmacology, SJ-30University of WashingtonSeattleUSA

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