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Voltage-Dependent Calcium Channels: Structure and Regulation in Normal and Abnormal States

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Molecular Basis of Membrane-Associated Diseases

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Abstract

Calcium (Ca) is an essential element for many cell processes. The major pathway by which Ca enters cells is through Ca channels located in cell membranes. Different types of Ca channels exist, and are generally classified as either voltage-dependent or receptor-dependent Ca channels. Voltage-dependent Ca channels are opened in response to a change in membrane potential, while receptor-dependent Ca channels are opened in response to the activation of an associated receptor. The subject of this review is a subclass of voltage-dependent Ca channels known as L-type or slow Ca channels [1–4]. These channels conduct a long-lasting current of large conductance [1] and are found in excitable (see refs. [2,3]) and nonexcitable [5] cells. L-type Ca channels are opened and closed in response to changes in membrane potential, but, in addition, they are regulated by receptor-dependent processes [3,6,7]. Considerable evidence from electrophy- siological studies suggests that L-type Ca channels are regulated by a cAMP- dependent phosphorylation event. In cardiac cells, any agent that elevates cAMP, such as β-adrenergic agonists, increases the probability of opening of L channels in response to a given change in membrane potential [6,7]. L-type Ca channels in other cells, including skeletal muscle [8,9], also are regulated by cAMP. Application of the purified catalytic subunit of cAMP-dependent protein kinase mimics the effects of cAMP [10, 11], and the inhibitor of this protein kinase prevents the effects [12]. Furthermore, the widely observed rundown of Ca channel activity over time in patch-clamp experiments has been slowed by cAMP-dependent protein kinase and ATP [13, 14]. Taken together, the results support the hypothesis that certain L channels are regulated by the cAMP-dependent phosphorylation of the channel itself or a regulatory protein. However, until recently biochemical evidence to support this hypothesis has been lacking because the protein(s) that comprise Ca channels were not known. Recently, considerable progress has been made in our understanding of the structure and biochemical properties of L channels, and insights into the biochemical events involved in the regulation of the channels is now possible. This review will focus on our current understanding of the structure and regulation of Ca channels. Disease-related defects in L-type Ca channels will also be addressed.

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References

  1. Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature (London) 316:440–443

    Article  CAS  Google Scholar 

  2. McCleskey EW, Fox AP, Feldman D, Tsien RW (1986) Different types of calcium channels. J Exp Biol 124:177–190

    PubMed  CAS  Google Scholar 

  3. Hosey MM, Lazdunski M (1988) Calcium channels: molecular pharmacology, structure and regulation. J Membrane Biol 104:81–105

    Article  CAS  Google Scholar 

  4. Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52

    Article  PubMed  CAS  Google Scholar 

  5. Chen C, Corbley MJ, Roberts TM, Hess P (1988) Voltage-sensitive calcium channels in normal and transformed 3T3 fibroblasts. Science 239:1024–1026

    Article  PubMed  CAS  Google Scholar 

  6. Reuter H (1983) Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature (London) 301:569–574

    Article  CAS  Google Scholar 

  7. Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC (1986) Mechanisms of calcium channel modulation by β-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol 18:691–710

    Article  PubMed  CAS  Google Scholar 

  8. Schmid A, Renaud J-F, Lazdunski M (1985) Short term and long term effects of β-adrenergic effectors and cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle. J Biol Chem 260:13041–13046

    PubMed  CAS  Google Scholar 

  9. Arreola J, Calvo J, Garcia MC, Sanchez JA (1987) Modulation of calcium channels of twitch skeletal muscle fibres of the frog by adrenaline and cyclic adenosine monophosphate. J Physiol 393:307–330

    PubMed  CAS  Google Scholar 

  10. Osterrieder W, Brum G, Hescheler J, Trautwein W, Flockerzi V, Hofmann F (1982) Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature (London) 298:576–578

    Article  CAS  Google Scholar 

  11. Brum G, Flockerzi V, Hofmann F, Osterrieder W, Trautwein W (1983) Injection of catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes. Pflüger’s Arch 398:147–154

    Article  CAS  Google Scholar 

  12. Bkaily G, Sperelakis N (1984) Injection of protein kinase inhibitor into cultured heart cells blocks slow calcium channels. Am J Physiol 246:H630–H634

    PubMed  CAS  Google Scholar 

  13. Chad JE, Eckert R (1986) An enzymatic mechanism for calcium current inactivation in dialyzed helix neurons. J Physiol 378:31–51

    PubMed  CAS  Google Scholar 

  14. Armstrong D, Eckert R (1987) Voltage-activated calcium channels that must be phosphorylated to respond to membrane depolarization. Proc Natl Acad Sci USA 84:2518–2522

    Article  PubMed  CAS  Google Scholar 

  15. Bean BP (1984) Nitrendipine block of cardiac calcium channels: high affinity binding to the inactivated state. Proc Natl Acad Sci USA 81:6388–6392

    Article  PubMed  CAS  Google Scholar 

  16. Sanguinetti MC, Kass RS (1984) Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res 55:336–348

    PubMed  CAS  Google Scholar 

  17. Cognard C, Romey G, Galizzi J-P, Fosset M, Lazdunski M (1986) Dihydropyridine-sensitive Ca channels in mammalian skeletal muscle in culture: electrophysical properties and interactions with Ca channel activator (Bay K 8644) and inhibitor (PN 200-100). Proc Natl Acad Sci USA 83:1518–1522

    Article  PubMed  CAS  Google Scholar 

  18. Kunze DL, Hamilton SL, Hawkes MJ, Brown AM (1987) Dihydropyridine binding and calcium channel function in clonal rat adrenal medullary tumor cells. Mol Pharmacol 31:401–409

    PubMed  CAS  Google Scholar 

  19. Fosset M, Jaimovich E, Delpont E, Lazdunski M (1983) [3H]Nitrendipine receptors in Skeletal muscle. J Biol Chem 258:6086–6092

    PubMed  CAS  Google Scholar 

  20. Glossmann H, Ferry DR, Boschek CB (1983) Purification of the putative calcium channel from skeletal muscle with the aid of [3H]-nimodipine binding. Naunyn-Schmiedeberg’s Arch Pharmacol 323:1–11

    Article  CAS  Google Scholar 

  21. Nicola-Siri L, Sanchez JA, Stefani E (1980) Effect of glycerol treatment on the calcium current of frog skeletal muscle. J Physiol (London) 305:87–96

    Google Scholar 

  22. Changeux J-P, Revah F (1987) The acetylcholine receptor molecule: allosteric sites and the ion channel. Trends Neurosci 10:245–250

    Article  CAS  Google Scholar 

  23. Catterall WA (1984) The molecular basis of neuronal excitability. Science 223:653–661

    Article  PubMed  CAS  Google Scholar 

  24. Striessnig J, Knaus H-G, Grabner M, Moosburger K, Scitz W, Lietz H, Glossmann H (1987) Photoaffinity labeling of phenylalkylamine receptor of the skeletal muscle transverse-tubule calcium channel. FEBS Lett 212:247–253

    Article  PubMed  CAS  Google Scholar 

  25. Leung AT, Imagawa T, Campbell KP (1987) Structural characterization of the 1,4-dihydropy-ridine receptor of the voltage-dependent Ca2+ channel from rabbit skeletal muscle. J Biol Chem 262:7943–7946

    PubMed  CAS  Google Scholar 

  26. Sieber M, Nastainczyk W, Zubor V, Wernet W, Hofmann F (1987) The 165-kD peptide of the purified skeletal muscle dihydropyridine receptor contains the known regulatory sites of the calcium channel. Eur J Biochem 167:117–122

    Article  PubMed  CAS  Google Scholar 

  27. Takahashi M, Seagar MJ, Jones JF, Reber BFX, Catterall WA (1987) Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci USA 84:5478–5482

    Article  PubMed  CAS  Google Scholar 

  28. Hosey MM, Barhanin J, Schmid A, Vandaele S, Ptasienski J, O’Callahan C, Cooper C, Lazdunski M (1987) Photoaffinity labelling and phosphorylation of a 165 kilodalton peptide associated with dihydropyridine and phenylalkylamine-sensitive calcium channels. Biochem Biophys Res Commun 147:1137–1145

    Article  PubMed  CAS  Google Scholar 

  29. Vaghy PL, Striessnig J, Miwa K, Knaus H-G, Itagaki K, McKenna E, Glossmann H, Schwartz A (1987) Identification of a novel 1, 4-dihydropyridine-and phenylalkylamine-binding polypeptide in calcium channel preparations. J Biol Chem 262:14337–14342

    PubMed  CAS  Google Scholar 

  30. Galizzi J-P, Borsotto M, Barhanin J, Fosset M, Lazdunski M (1986) Characterization and photoaffinity labeling of receptor sites for the Ca2+ channel inhibitors d-cis-diltiazem, (±)-be-pridil, desmethoxyverapamil, and ( + )-PN 200-110 in skeletal muscle transverse tubule membranes. J Biol Chem 261:1393–1397

    PubMed  CAS  Google Scholar 

  31. Sharp AH, Imagawa T, Leung AT, Campbell KP (1987) Identification and characterization of the dihydropyridine-binding subunit of the skeletal muscle dihydropyridine receptor. J Biol Chem 262:12309–12315

    PubMed  CAS  Google Scholar 

  32. Borsotto M, Barhanin J, Fosset M, Lazdunski M (1985) The 1,4-dihydropyridine receptor associated with the skeletal muscle voltage-dependent Ca2+ channel. J Biol Chem 26:14255–14263

    Google Scholar 

  33. Curtis BM, Catterall WA (1984) Purification of the calcium antagonist receptor of the voltage-sensitive calcium channel from skeletal muscle transverse tubules. Biochemistry 23:2113–2118

    Article  PubMed  CAS  Google Scholar 

  34. Flockerzi V, Oekem H-J, Hofmann F, Pelzer D, Cavalié A, Trautwein W (1986) Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Nature (London) 323:66–68

    Article  CAS  Google Scholar 

  35. Smith JS, McKenna EJ, Ma J, Vilven J, Vaghy PL, Schwartz A, Coronado R (1987) Calcium channel activity in a purified dihydropyridine-receptor preparation of skeletal muscle. Biochemistry 26:7182–7188

    Article  PubMed  CAS  Google Scholar 

  36. Talvenheimo JA, Worley JF, Nelson MT (1987) Heterogeneity of calcium channels from a purified dihydropyridine receptor preparation. Biophys J 52:891–899

    Article  PubMed  CAS  Google Scholar 

  37. Barhanin J, Coppola T, Schmid A, Borsotto M, Lazdunski M (1987) The calcium channel antagonists receptor from rabbit skeletal muscle. Eur J Biochem 164:525–531

    Article  PubMed  CAS  Google Scholar 

  38. Curtis BM, Catterall WA (1986) Reconstitution of the voltage-sensitive calcium channel purified from skeletal muscle transverse tubules. Biochemistry 25:3077–3083

    Article  PubMed  CAS  Google Scholar 

  39. Home WA, Ghany MA, Racker E, Weiland GA, Oswald RE, Cerione RA (1988) Functional reconstitution of skeletal muscle Ca2+ channels: separation of regulatory and channel components. Proc Natl Acad Sci USA 85:3718–3722

    Article  Google Scholar 

  40. Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature (London) 328:313–318

    Article  CAS  Google Scholar 

  41. Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N, Kangawa K, Matsuo H, Raftery MA, Hirose T, Inayama S, Hayashida H, Miyata T, Numa S (1984) Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence. Nature (London) 312:121–127

    Article  CAS  Google Scholar 

  42. Noda M, Takayuki I, Kayano T, Suzuki H, Takeshima H, Kurasaki M, Takahashi H, Numa S (1986) Existence of distinct sodium channel messenger RNAs in rat brain. Nature (London) 320:188–192

    Article  CAS  Google Scholar 

  43. Leung AT, Imagawa T, Block B, Franzini-Armstrong C, Campbell KP (1988) Biochemical and ultrastructural characterization of the 1, 4-dihydropyridine receptor from rabbit skeletal muscle. J Biol Chem 263:994–1001

    PubMed  CAS  Google Scholar 

  44. Morton ME, Froehner SC (1987) Monoclonal antibody identifies a 200-kDa subunit of the dihydropyridine-sensitive calcium channel. J Biol Chem 262:11904–11907

    PubMed  CAS  Google Scholar 

  45. Cognard C, Lazdunski M, Romey G (1986) Different types of Ca2+ channels in mammalian skeletal muscle cells in culture. Proc Natl Acad Sci USA 83:517–521

    Article  PubMed  CAS  Google Scholar 

  46. Rosenberg RL, Hess P, Reeves JP, Smilowitz H, Tsien RW (1986) Calcium channels in planar lipid bilayers: insights into mechanisms of ion permeation and gating. Science 231:1564–1566

    Article  PubMed  CAS  Google Scholar 

  47. Cooper CL, Vandaele S, Barhanin J, Fosset M, Lazdunski M, Hosey MM (1987) Purification and characterization of the dihydropyridine-sensitive voltage-dependent calcium channel from cardiac tissue. J Biol Chem 262:509–512

    PubMed  CAS  Google Scholar 

  48. Chang FC, Hosey MM (1988) Dihydropyridine and phenylalkylamine receptors associated with cardiac and skeletal muscle calcium channels are structurally different. J Biol Chem 263:18929–18937

    PubMed  CAS  Google Scholar 

  49. O’Callahan CM, Hosey MM (1988) Multiple phosphorylation sites in the 165-kilodalton peptide associated with dihydrophyridine-sensitive calcium channels. Biochemistry 27:6071–6077

    Article  PubMed  Google Scholar 

  50. Hosey MM, Borsotto M, Lazdunski M (1986) Phosphorylation and dephosphorylation of dihy-dropyridine-sensitive voltage-dependent Ca2+ channel in skeletal muscle membranes by cAMP-and Ca2+-dependent processes. Proc Natl Acad Sci USA 83:3733–3737

    Article  PubMed  CAS  Google Scholar 

  51. Marchetti C, Brown AM (1988) Protein kinase activator 1-oleoyl-2-acetyl-sn-glycerol inhibits two types of calcium currents in GH3 cells. Am J Physiol 254:C206–C210

    PubMed  CAS  Google Scholar 

  52. Dosemeci A, Dhallan RS, Cohen NM, Lederer WJ, Rogers TB (1988) Phorbol ester increases calcium current and stimulates the effects of angiotensin II on cultured and neonatal rat heart myocytes. Circ Res 62:347–357

    PubMed  CAS  Google Scholar 

  53. Rane SG, Dunlap K (1986) Kinase C activator 1, 2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons. Proc Natl Acad Sci USA 83:184–188

    Article  PubMed  CAS  Google Scholar 

  54. DiVirgilio F, Pozzan T, Wolheim CB, Vincentini LM, Meldolesi J (1986) Tumor promoter phorbol myristate acetate inhibits Ca2+ influx through voltage-gated Ca2+ channels in two secretory cell lines PC12 and RINm5F. J Biol Chem 261:32–35

    CAS  Google Scholar 

  55. O’Callahan CM, Ptasienski J, Hosey MM (1988) Phosphorylation of the 165 kDa dihydro-pyridine/phenylalkylamine receptor from skeletal muscle by protein kinase. C J Biol Chem 263:17342–17349

    Google Scholar 

  56. Curtiz BM, Catterall WA (1985) Phosphorylation of the calcium antagonist receptor of the voltage-sensitive calcium channel by cAMP-dependent protein kinase. Proc Natl Acad Sci USA 82:2528–2532

    Article  Google Scholar 

  57. Lossnitzer K (1975) Genetic induction of a cardiomyopathy. Handbook of experimental pharmacology, vol 16, Springer Berlin Heidelberg New York, pp 309–344

    Google Scholar 

  58. Rouleau JL, Chuck LHS, Hollosi G, Kidd P, Sievers RE, Wikman-Coffelt J, Parmley WW (1982) Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster. Circ Res 50:405–412

    PubMed  CAS  Google Scholar 

  59. Wagner JA, Reynolds IJ, Weisman HF, Dudeck P, Weisfeldt ML, Snyder SH (1986) Calcium antagonist receptors in cardiomyopathic hamster: selective increases in heart, muscle, brain. Science 232:515–518

    Article  PubMed  CAS  Google Scholar 

  60. Pincon-Raymond M, Rieger F, Fosset M, Lazdunski M (1985) Abnormal transverse tubule system and abnormal amount of receptors for Ca2+ channel inhibitors of the dihydropyridine family in skeletal muscle from mice with embryonic muscular dysgenesis. Dev Biol 112:458–466

    Article  PubMed  CAS  Google Scholar 

  61. Romey G, Rieger F, Renaud JF, Pincon-Raymond M, Lazdunski M (1986) The electrophysical expression of Ca2+ channels and of apamin sensitive Ca2+ activated K+ channels is abolished in skeletal muscle cells from mice with muscular dysgenesis. Biochem Biophys Res Commun 136:935–940

    Article  PubMed  CAS  Google Scholar 

  62. Beam KG, Knudson CM, Powell JA (1986) A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells. Nature (London) 320:168–170

    Article  CAS  Google Scholar 

  63. Rieger F, Bournaud R, Shimahara T, Garcia L, Pincon-Raymond M, Romey G, Lazdunski M (1987) Restoration of dysgenic muscle contraction and calcium channel function by co-culture with normal spinal cord neurons. Nature (London) 330:563–566

    Article  CAS  Google Scholar 

  64. Fukunoya H, Engel AG, Lang B, Newson-Davis J, Vincent A (1983) Passive transfer of Lambert-Eaton myasthenie syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci USA 80:7636–7640

    Article  Google Scholar 

  65. Kim YI, Neher E (1988) IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels. Science 239:405–408

    Article  PubMed  CAS  Google Scholar 

  66. Lambert EH, Elmqvist D (1971) Quantal components of end-plate potentials in the myasthenie syndrome. Ann NY Acad Sci 183:183–199

    Article  PubMed  CAS  Google Scholar 

  67. Renaud J-F, Schmid A, Romey G, Nana JL, Lazdunski M (1986) Melvinolin, an inhibitor of cholesterol biosynthesis, drastically depresses Ca2 + channel activity and uncouples excitation from contraction in cardiac cells in culture. Proc Natl Acad Sci USA 83:8007–8011

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular and Cellular Biochemistry, University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL, 60064, USA

    M. M. Hosey, F. C. Chang, C. M. O’Callahan & J. Ptasienski

  2. Centre de Biochimie du CNRS, Université de Nice, Parc Valrose, 06034, Nice, France

    J. Barhanin & M. Lazdunski

  3. Department of Pharmacology, Northwestern University Medical School, 303 E Chicago Ave, Chicago, JL, 60611, Czech Republic

    M. M. Hosey

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  1. M. M. Hosey
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  2. F. C. Chang
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  3. C. M. O’Callahan
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  4. J. Ptasienski
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  5. J. Barhanin
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  6. M. Lazdunski
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Editors and Affiliations

  1. Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstraße 28, CH-3012, Bern, Switzerland

    Angelo Azzi

  2. Institute of Physiology, Czechoslovak Academy of Sciences, Videnska 1083, CS-142 20, Praha 4, Czech Republic

    Zdenek Drahota

  3. Institute of Medical Biochemistry and Chemistry, University of Bari, Piazza G. Cesare, I-70124, Bari, Italy

    Sergio Papa

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© 1989 Springer-Verlag Berlin Heidelberg

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Hosey, M.M., Chang, F.C., O’Callahan, C.M., Ptasienski, J., Barhanin, J., Lazdunski, M. (1989). Voltage-Dependent Calcium Channels: Structure and Regulation in Normal and Abnormal States. In: Azzi, A., Drahota, Z., Papa, S. (eds) Molecular Basis of Membrane-Associated Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74415-0_11

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