Pharmacological Properties of the Chromaffin Cell Calcium Channel

  • A. G. Garcia
  • C. R. Artalejo
  • R. Borges
  • J. A. Reig
  • F. Sala
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 211)


In 1961, Douglas and Rubin21 concluded that “the role of acetylcholine as a transmitter at the adrenal medulla is to cause some brief change in medullary cells which allows extracellular Ca2+ to penetrate them and trigger the catecholamine ejection process.” The formation accumulated since then can be summarized in the diagram of the sequence of events taking place during the secretory cycle depicted in Fig. 1.


Chromaffin Cell Adrenal Medulla Secretory Response Catecholamine Release Catecholamine Secretion 
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  1. 1.
    J. Aguirre, J. Falute, J.E.B. Pinto, and J.M. Trifaro, Effects of methoxyverapamil on the stimulation by Ca2+, Sr2+ and inhibition by Mg on catecholamine release from the adrenal medulla, Br. J. Pharmac. 66:591 (1979).CrossRefGoogle Scholar
  2. 2.
    J. Aguirre, J.E.B. Pinto, and J.M. Trifaro, Calcium movements during the release of the catecholamines from the adrenal medulla: effects of methoxyverapamin and external cations, J. Physiol. 269:371 (1977).PubMedGoogle Scholar
  3. 3.
    L. Arqueros and A.J. Daniels, Analysis of the inhibitory effect of verapamil on the adrenal medullary secretion, Life Sci. 23:2415 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    L. Arqueros and A.J. Daniels, Manganese as agonist and antagonist of calcium ions: dual effect upon catecholamine release from adrenal medulla, Life Sci. 28:1535 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    P.F. Baker and D.E. Knight, Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes, Nature 276:620 (1978).PubMedCrossRefGoogle Scholar
  6. 6.
    P.F. Baker and D.E. Knight, Calcium control of exocytosis in bovine adrenal medullary cells, TINS 7:120 (1984).Google Scholar
  7. 7.
    B. Biales, M. Dichter, and A. Tischler, Electrical excitability of adrenal chromaffin cells, J. Physiol. 262:743 (1976).PubMedGoogle Scholar
  8. 8.
    J.L. Borowitz, Effect of lanthanum on catecholamine release from adrenal medulla, Life Sci, Part I 11:959 (1972).CrossRefGoogle Scholar
  9. 9.
    B.L. Brandt, S. Hagiwara, Y. Kodokoro, and S. Miyazaki, Action potentials in the rat chromaffin cell and effects of acetylcholine, J. Physiol. 263:417 (1976).PubMedGoogle Scholar
  10. 10.
    P.D. Bregestovski, R. Miledi, and I. Parker, Calcium conductance of acetylcholine-induced endplate channels, Nature 279:638 (1979).PubMedCrossRefGoogle Scholar
  11. 11.
    P. Brehm and R. Eckert, Calcium entry leads to inactivation of calcium channel in Paramecium, Science 202:1203 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    A.M. Brown, D.L. Kunze, and A. Yatani, The agonist effect of dihydropyridines on Ca channels, Nature 311:570 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    R.D. Burgoyne and T.R. Cheek, Is the transient nature of the secretory response of chromaffin cells due to inactivation of calcium channels?, FEBS Lett. 182:115 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    M.H. Carvalho, J.C. Prat, A.G. Garcia, and S.M. Kirpekar, Ionomycin stimulates secretion of catecholamines from cat adrenal gland and spleen, Am. J Physiol. 242:E137 (1982).PubMedGoogle Scholar
  15. 15.
    V. Cena, G.P. Nicolas, P. Sanchez-Garcia, S.M. Kirpekar, and A.G. Garcia, Pharmacological dissection of receptor-associated and voltage-sensitive ionic channels involved in catecholamine release, Neuroscience 10:1455 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    D.E. Clapham and E. Neher, Trifluoperazine reduces inward ionic currents and secretion by separate mechanisms in bovine chromaffin cells, J. Physiol. 353:541 (1984).PubMedGoogle Scholar
  17. 17.
    W.W. Douglas and T. Kanno, The effect of amethocaine on acetylcholine induced depolarization and catecholamine secretion in the adrenal chromaffin cell, Br. J. Pharmac. 30:612 (1967).Google Scholar
  18. 18.
    W.W. Douglas, T. Kanno, and S.R. Sampson, Effects of acetylcholamine and other medullary secretagogues and antagonists on the membrane potential of adrenal chromaffin cells: an analysis employing techniques of tissue culture, J Physiol. 118:107 (1967).Google Scholar
  19. 19.
    W.W. Douglas and A.M. Poisner, On the mode of action of acetylcholine in evoking adrenal medullary secretion: Increased uptake of calcium during the secretory response, J. Physiol. 162:385 (1962).PubMedGoogle Scholar
  20. 20.
    W.W. Douglas and A.M. Poisner, Preferential release of adrenaline from the adrenal medula by muscarine and pilocarpine, Nature 208:1102 (1965).PubMedCrossRefGoogle Scholar
  21. 21.
    W.W. Douglas and R.P. Rubin, The role of calcium in the secretory response of the adrenal medulla to acetylcholine, J Physiol. 159:40 (1961).PubMedGoogle Scholar
  22. 22.
    W.W. Douglas and R.P. Rubin, The mechanism of catecholamine release from the adrenal medulla and the role of calcium in stimulus-secretion coupling, J. Physiol. 167:288 (1963).PubMedGoogle Scholar
  23. 23.
    W.W. Douglas and R.P. Rubin, The effects of alkaline earths and other divalent cations on adrenal medullary secretion, J. Physiol. 175:231 (1964).PubMedGoogle Scholar
  24. 24.
    R. Eckert and J.E. Chad, Inactivation of Ca channels, Prog. Biophys. Molec. Biol. 44:215 (1984).CrossRefGoogle Scholar
  25. 25.
    E. El-Fakahany and E. Richelson, Effect of some calcium antagonists on muscarinic receptor-mediated cyclic GMP formation, J. Neurochem. 40:705 (1983).PubMedCrossRefGoogle Scholar
  26. 26.
    E.M. Fenwick, A. Marty, and E. Neher, A patch clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine, J. Physiol. 331:577 (1982).PubMedGoogle Scholar
  27. 27.
    E.M. Fenwick, A. Marty, and E. Neher, Sodium and calcium channels in bovine chromaffin cells, J Physiol. 331:599 (1982).PubMedGoogle Scholar
  28. 28.
    A. Fleckenstein, Die Bedentung der energiereichen Phosphate fur Kontraktilitat und Tonus des Myokards, Verh. DtschGes. Inn. Med. 70:81 (1964).Google Scholar
  29. 29.
    A. Fleckenstein, Specific pharmacology fo calcium in myocardium cardiac pacemakers and vascular smooth muscle, Ann. Rev. Pharmac. Toxicol. 17:149 (1977).CrossRefGoogle Scholar
  30. 30.
    A.M. Galzin and S.Z. Langer, Presynaptic alpha2 adrenoceptor antagonism by verapamil but not by diltiazem in rabbit hypothelamic slices, Br. J Pharmac. 78:571 (1983).CrossRefGoogle Scholar
  31. 31.
    A.G. Garcia, S.M. Kirpekar, and J.C. Prat, A calcium ionophore stimulating the secretion of catecholamines from the cat adrenal, J. Physiol. 244:253.(1983)Google Scholar
  32. 32.
    A.G. Garcia, V. Cena, and J. Frias, Pharmacological dissection of ionic channels involved in catecholamine release from the chromaffin cell, Actual. Chim. Ther. 11° serie, 165 (1984).Google Scholar
  33. 33.
    A.G. Garcia, F. Sala, M.G. Ladona, V. Cena, and C. Montiel, Analysis of the catecholamine secretory process by using a novel dihydropyridine calcium “agonist” and potassium or calcium gradients, in: “Regulation of Transmitter Function”, W.S. Vizi and K. Magyar, eds., Amsterdam, Elsevier (1984).Google Scholar
  34. 34.
    A.G. Garcia, F. Sala, J.A. Reig, S. Viniegra, J. Frias, R. Fonteriz, and L. Gandia, Dihydropyridine Bay-K-8644 activates chromaffin cell calcium channels, Nature 309:69 (1984).PubMedCrossRefGoogle Scholar
  35. 35.
    A.G. Garcia, F. Sala, V. Cena, C. Montiel, and M.G. Ladona, Modulation by calcium of the kinetics of the chromaffin cell secretory response, in: “Stimulus-secretion Coupling n Chromaffin Cells”, K. Rosenheck, ed., Boca Raton, Florida, CRC Press (in press).Google Scholar
  36. 36.
    S. Hagiwara and L. Byerly, Calcium Channel, Ann. Rev. Neurosci. 4:69 (1981).PubMedCrossRefGoogle Scholar
  37. 37.
    P. Hess, J.B. Lansman, and R.W. Tsien, Different modes of Ca channels gating behaviour favoured by dihydropyridine Ca agonists and antagonists, Nature 311:538 (1984).PubMedCrossRefGoogle Scholar
  38. 38.
    R.W. Holz, R.A. Senter, and R.A. Frye, Relationship between Ca2+ uptake and catecholamine secretion in primary dissociated cultures of adrenal medulla, J. Neurochem. 39:635 (1982).PubMedCrossRefGoogle Scholar
  39. 39.
    T. Hoshi, J. Rothlein, and S.J. Smith, Facilitation of Ca2+ -channel currents in bovine adrenal chromaffin cells, Proc. Natl. Acad. Sci. USA 81:5871 (1984).PubMedCrossRefGoogle Scholar
  40. 40.
    K. Ishikawa and T. Kanno, Influences of extracellular calcium and potassium concentrations on adrenaline release and membrane potential in the perfused adrenal medulla of the rat, Jap. J. Physiol. 28:275 (1978).CrossRefGoogle Scholar
  41. 41.
    Y. Kidokoro, Electrophysiology f adrenal chromaffin cells, in: “The Electrophysiology of the Secretory Cell”, A.M. Poisner and J.M. Trifaro, eds., Elsevier Science Publishers B.V., Amsterdam (1985).Google Scholar
  42. 42.
    Y. Kidokoro and A.K. Ritchie, Chromaffin cell action potentials and their possible role in adrenaline secretion from rat adrenal medulla, J. Physiol. 307:199 (1980).PubMedGoogle Scholar
  43. 43.
    Y. Kodokoro, S. Miyazaki, and S. Ozawa, Acetylcholine-induced membrane depolarization and potential fluctuations in the rat adrenal chromaffin cell, J Physiol. 324:203 (1982).Google Scholar
  44. 44.
    D.L. Kilpatrick, R.J. Slepetis, J.J. Corcoran, and N. Kirshner, Calcium uptake and catecholamine secretion by cultured bovine adrenal medulla cells, J. Neurochem. 38:427 (1982).PubMedCrossRefGoogle Scholar
  45. 45.
    S.M. Kirpekar, J.C. Prat, and M.T. Schiavone, Effect of muscarine on the release of catecholamines from the perfused adrenal gland of the cat, Br. J Pharmac. 77:455 (1982).CrossRefGoogle Scholar
  46. 46.
    S. Kitayama, K. Morita, T. Dohi, and A. Tsujimoto, The nature of the stimulatory action of gamma-aminobutyric acid in the isolated perfused dog adrenals, Naunyn-Schmiedeberg’s Arch. Pharmacol. 326:106 (1984).CrossRefGoogle Scholar
  47. 47.
    D.E. Knight and N.T. Kesteven, Evoked transient intracellular free Ca2+ changes and secretion in isolated bovine adrenal medullary cells, Proc. Roy. Soc. London B. 218:177 (1983).CrossRefGoogle Scholar
  48. 48.
    S. Kokubun and H. Reuter, Dihydropyridine derivates prolong the open state of Ca channels in cultured cardiac cells, Proc. Natl. Acad. Sci. USA 81:4824 (1984).PubMedCrossRefGoogle Scholar
  49. 49.
    S. Lemaire, G. Derome, R. Tseng, P. Mercier and I. Lemaire, Distinct regulations by calcium of cyclic GMP levels and catecholamne secretion in isolated bovine adrenal chromaffin cells, Metabolism 30:462 (1981).PubMedCrossRefGoogle Scholar
  50. 50.
    A. Marty, Ca2+ -dependent K+ channels with large unitary conductance in chromaffin cell membranes, Nature 291:497 (1981).PubMedCrossRefGoogle Scholar
  51. 51.
    C. Montiel, A.R. Artalejo, and A.G. Garcia, Effects of the novel dihydropyridine Bay-K-8644 on adrenomedullary catecholamine release evoked by calcium reintroduction, Biochem. Biophys. Res. Comm. 120:851 (1984).PubMedCrossRefGoogle Scholar
  52. 52.
    U.A. Nachshen and M.R. Blaustein, Influx of calcium, strontium and barium in presynaptic nerve endings, J. Gen. Physiol. 79:1065 (1982).PubMedCrossRefGoogle Scholar
  53. 53.
    P.J. Norris, U.K. Dhaltiwal, D.P. Druce and H.F. Bradford, The suppression of stimulus-evoked release of amino acid neurotransmitters from synaptosomes by verapamil, J. Neurochem. 40:514 (1983).PubMedCrossRefGoogle Scholar
  54. 54.
    J.E.B. Pinto and J.M. Trifaro, The different effects of D-600 (methoxy-verapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation, Br. J Pharmac. 57:127 (1976).CrossRefGoogle Scholar
  55. 55.
    H. Sasakawa, K, Kumamura, S. Yamamoto, and R. Kato, Effects of W-7 on catecholamine release and 45Ca2+ uptake in cultured adrenal chromaffin cells, Life Sci. 33:2017 (1983).PubMedCrossRefGoogle Scholar
  56. 56.
    A.S. Schneider, H.T. Cline, K. Rosenheck, and M. Sonenberg, Stimulus-secretion coupling in isolated adrenal chromaffin cells: calcium channel activation and possible role of cytoskeletal elements, J. Neurochem. 37:567 (1981).PubMedCrossRefGoogle Scholar
  57. 57.
    M. Schramm, G. Thomas, R. Towart, and G. Franckowiak, Novel dihydropyridines with positive iontropic action through activation of Ca2+ channels, Nature 303:535 (1983).PubMedCrossRefGoogle Scholar
  58. 58.
    S.M. Simon and R.R. Llinas, Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release, Biophys. J. 48:485 (1985).PubMedCrossRefGoogle Scholar
  59. 59.
    J. Sorimachi and S. Nishimura, Operation of internal Na-dependent Ca influx mechanism associated with catecholamine secretion in the adrenal chromaffin cells, Jap. J. Physiol. 34:19 (1984).CrossRefGoogle Scholar
  60. 60.
    M. Spedding, Calcium antagonist subgroups, TIPS 6:109 (1985).Google Scholar
  61. 61.
    M. Takahashi and A. Ogura, Dihydropyridines as potent calcium channel blockers in neuronal cells, FEBS Lett. 152:191 (1983).PubMedCrossRefGoogle Scholar
  62. 62.
    D. Tillotson, Inactivation of Ca conductance dependent on entry of Ca ions in molluscan neurons, Proc. Natl. Acad. Sci. USA 76:1497 (1979).PubMedCrossRefGoogle Scholar
  63. 63.
    R.W. Tsien, Calcium channels in excitable cell membranes, Ann. Rev. Physiol. 45:341 (1983).CrossRefGoogle Scholar
  64. 64.
    A. Wada, N. Yanagihara, F. Izumi, S. Sakurai, and H. Kobayashi, Trifluoperazine inhibits 45Ca2+ uptake and catecholamine secretion and synthesis in adrenal medullary cells, J. Neurochem. 40:481 (1983).PubMedCrossRefGoogle Scholar
  65. 65.
    A. Wada, H. Takara, F. Izumi, H. Kobayashi, and N. Yanagihara, Influx of 22Na through acetylcholine receptor-associated Na channels: Relationship between Na influx, 45Ca influx and secretion of catecholamines in cultured bovine adrenal medulla cells, Neuroscience 15:283 (1985).PubMedCrossRefGoogle Scholar
  66. 66.
    A.R. Wakade, Studies on secretion of catecholamines evoked by acetylcholine or transmural stimulation of the rat adrenal gland, J Physiol. 313:463 (1981).PubMedGoogle Scholar
  67. 67.
    G. Yellen, Ionic permeation and blockade in Ca2+-activated K channels of bovine chromaffin cells, J. Gen. Physiol. 84:157 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • A. G. Garcia
    • 1
  • C. R. Artalejo
    • 1
  • R. Borges
    • 1
  • J. A. Reig
    • 1
  • F. Sala
    • 1
  1. 1.Departamento de Farmacologia, Facultad de MedicinaUniversidad de AlicanteEspanaSpain

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