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Excitable Tissues

The Heart
  • Richard W. Tsien
  • Peter Hess

Abstract

Cardiac action potentials serve many purposes. They form the cellular basis for pacemaker activity, impulse spread, and control of cardiac contraction. Despite this variety of functions, there are ample reasons for believing that impulses in cardiac cells follow the same general principles as in other excitable tissues. The preceding chapters on nerve and muscle have provided a useful foundation for understanding action potentials in the heart. We shall draw upon such similarities, but shall also focus on the unique aspects of cardiac activity.

Keywords

Voltage Dependence Cardiac Cell Slow Response Voltage Clamp Purkinje Fiber 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    McNutt, N. S., and R. S. Weinstein. 1973. Membrane ultrastructure at mammalian intercellular junctions. Prog. Biophys. Mol. Biol. 26:45–101.PubMedGoogle Scholar
  2. 2.
    Barr, L., M. M. Dewey, and W. Berger. 1965. Propagation of action potentials and the structure of the nexus in cardiac muscle. J. Gen. Physiol. 48:797–823.PubMedGoogle Scholar
  3. 3.
    Dreifuss, J. J., L. Girardier, and W. G. Forssmann. 1966. Étude de la propagation de l’éxcitation dans le ventricle de rat au moyen de solutions hypertoniques. Pfluegers Arch. 292:13–33.Google Scholar
  4. 4.
    Kawamura, K., and T. Konishi. 1967. Ultrastructure of the cell junction of heart muscle with special reference to its functional significance in excitation conduction and to the concept of “disease of intercalated disc.” Jpn. Circ. J. 31:1533–1543.PubMedGoogle Scholar
  5. 5.
    Gilula, N. B. 1974. Junctions between cells. In: Cell Communication. R. P. Cox, ed. Wiley, New York.Google Scholar
  6. 6.
    Unwin, P. N. T., and G. Zampighi. 1980. Structure of the junction between communicating cells. Nature (London) 283:545–549.Google Scholar
  7. 7.
    Unwin, P. N. T., and P. D. Ennis. 1984. Two configurations of a channel-forming protein. Nature (London) 307:609–613.Google Scholar
  8. 8.
    Weidmann, S. 1966. The diffusion of radiopotassium across intercalated disks of mammalian cardiac muscle. J. Physiol. (London) 187:323–342.Google Scholar
  9. 9.
    Weingart, R. 1974. The permeability to tetraethylammonium ions of the surface membrane and the intercalated disks of sheep and calf myocardium. J. Physiol. (London) 240:741–762.Google Scholar
  10. 10.
    Imanaga, I. 1974. Cell to cell diffusion of procion yellow in sheep and calf Purkinje fibres. J. Membr. Biol. 16:381–388.PubMedGoogle Scholar
  11. 11.
    Pollack, G. H. 1976. Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart. J. Physiol. (London) 255:275–298.Google Scholar
  12. 12.
    Weidmann, S. 1970. Electrical constants of trabecular muscle from mammalian heart. J. Physiol. (London) 210:1041–1054.Google Scholar
  13. 13.
    Kushmerick, M. J., and R. J. Podolsky. 1969. Ionic mobility in muscle cells. Science 166:1297–1298.PubMedGoogle Scholar
  14. 14.
    Matter, A. 1973. A morphometric study on the nexus of rat cardiac muscle. J. Cell Biol. 56:690–696.PubMedGoogle Scholar
  15. 15.
    Rose, B., and W. R. Loewenstein. 1975. Permeability of cell junction depends on local cytoplasmic calcium activity. Nature (London) 254:250–252.Google Scholar
  16. 16.
    Dahl, G., and G. Isenberg. 1980. Decoupling of heart muscle cells: Correlation with increased cytoplasmic calcium activity and with changes of nexus ultrastructure. J. Membr. Biol. 53:63–75.PubMedGoogle Scholar
  17. 17.
    Reber, W. R., and R. Weingart. 1982. Ungulate cardiac Purkinje fibers: The influence of intracellular pH on the electrical cell-to-cell coupling. J. Physiol. (London) 328:87–104.Google Scholar
  18. 18.
    De Mello, W. C. 1980. Influence of intracellular injection of H+ on the electrical coupling in cardiac Purkinje fibers. Cell. Biol. Int. Rep. 4:51–58.PubMedGoogle Scholar
  19. 19.
    Spray, D. C., J. H. Stern, A. L. Harris, and M. V. Bennett. 1982. Gap junctional conductance: Comparison of sensitivities to H and Ca ions. Proc. Natl. Acad. Sci. USA 79:441–445.PubMedGoogle Scholar
  20. 20.
    White, R. L., A. C. Carvalho, D. C. Spray, B. A. Wittenberg, and M. V. L. Bennett. 1983. Gap junctional conductance between isolated pairs of ventricular myocytes from rat. Biophys. J. 41:217a.Google Scholar
  21. 21.
    Weidmann, S. 1952. The electrical constants of Purkinje fibres. J. Physiol. (London) 115:227–236.Google Scholar
  22. 22.
    Bonke, F. I. M. 1973. Electrotonic spread in the sinoatrial node of the rabbit heart. Pfluegers Arch. 339:17–23.Google Scholar
  23. 23.
    Woodbury, J. W., and W. E. Crill. 1961. On the problem of impulse conduction in the atrium. In: Nervous Inhibition. E. Florey, ed. Pergamon Press, Elmsford, N.Y. pp. 124–135.Google Scholar
  24. 24.
    Draper, M. H., and M. Mya-Tu. 1959. A comparison of the conduction velocity in cardiac tissues of various mammals. Q. J. Exp. Physiol. 44:91–109.Google Scholar
  25. 25.
    Sano, T., N. Takayama, and T. Shimamoto. 1959. Directional difference of conduction velocity in the cardiac ventricular syncytium studied by microelectrodes. Circ. Res. 7:262–267.PubMedGoogle Scholar
  26. 26.
    Clerc, L. 1976. Directional differences of impulse spread in trabecular muscle from mammalian heart. J. Physiol. (London) 255:335–346.Google Scholar
  27. 27.
    Woodbury, J. W. 1962. Cellular electrophysiology of the heart. In: Handbook of Physiology, Section 2, Volume 1. W. F. Hamilton and P. Dow, eds. American Physiological Society, Washington, D.C. pp. 237–238.Google Scholar
  28. 28.
    Hodgkin, A. L. 1951. The ionic basis of electrical activity in nerve and muscle. Biol. Rev. 26:339–409.Google Scholar
  29. 29.
    Draper, M. H., and S. Weidmann. 1951. Cardiac resting and action potentials recorded with an intracellular electrode. J. Physiol. (London) 115:74–94.Google Scholar
  30. 30.
    Del Castillo, J., and J. W. Moore. 1959. On increasing the velocity of a nerve impulse. J. Physiol. (London) 148:665–670.Google Scholar
  31. 31.
    Weingart, R. 1977. The actions of ouabain on intercellular coupling and conduction velocity in mammalian ventricular muscle. J. Physiol. (London) 264:341–365.Google Scholar
  32. 32.
    Tsien, R. W., and R. Weingart. 1976. Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut-end method. J. Physiol. (London) 260:117–141.Google Scholar
  33. 33.
    Hoffman, B. F., and P. F. Cranefield. 1960. Electrophysiology of the Heart. McGraw-Hill, New York.Google Scholar
  34. 34.
    Hogan, P. M., and L. D. Davis. 1968. Evidence for specialized fibers in the canine right atrium. Circ. Res. 23:387–396.PubMedGoogle Scholar
  35. 35.
    Mendez, C., and G. K. Moe. 1972. Atrioventricular transmission. In: Electrical Phenomena in the Heart. W. C. De Mello, ed. Academic Press, New York.Google Scholar
  36. 36.
    Cranefield, P. F. 1975. The Conduction of the Cardiac Impulse. Futura, Mount Kisco, N.Y.Google Scholar
  37. 37.
    Carmeliet, E., and J. Vereecke. 1980. Electrogenesis of the action potential and automaticity. In: Handbook of Physiology, Volume I. R. M. Berne, ed. American Physiological Society, Washington, D.C. pp. 269–334.Google Scholar
  38. 38.
    Piwnica-Worms, D., R. Jacob, C. R. Horres, and M. Lieberman. 1983. Transmembrane chloride flux in tissue-cultured chick heart cells. J. Gen. Physiol 81:731–748.PubMedGoogle Scholar
  39. 39.
    Dudel, J., K. Peper, R. Rüdel, and W. Trautwein. 1967. The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pfluegers Arch. 295:213–226.Google Scholar
  40. 40.
    Johnson, E. A., and M. Lieberman. 1971. Heart: Excitation and contraction. Annu. Rev. Physiol. 33:479–532.PubMedGoogle Scholar
  41. 41.
    Reuter, H. 1979. Properties of two inward membrane currents in the heart. Annu. Rev. Physiol. 41:413–424.PubMedGoogle Scholar
  42. 42.
    Colatsky, T. J., and R. W. Tsien. 1979. Sodium channels in rabbit cardiac Purkinje fibers. Nature (London) 278:265–268.Google Scholar
  43. 43.
    Colatsky, T. J. 1980. Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibers. J. Physiol. (London) 305:215–234.Google Scholar
  44. 44.
    Ebihara, L., N. Shigeto, M. Lieberman, and E. A. Johnson. 1980. The initial inward current in spherical clusters of chick embryonic heart cells. J. Gen. Physiol. 75:437–456.PubMedGoogle Scholar
  45. 45.
    Lee, K. S., T. A. Weeks, R. L. Kao, N. Akaike, and A. M. Brown. 1979. Sodium current in single heart muscle cells. Nature (London) 278:269–271.Google Scholar
  46. 46.
    Brown, A. M., K. S. Lee, and T. Powell. 1981. Sodium current in single rat heart muscle cells. J. Physiol. (London) 318:479–500.Google Scholar
  47. 47.
    Bodewei, R., S. Hering, B. Lemke, L. V. Rosenshtraukh, A. I. Undrovinas, and A. Wollenberger. 1982. Characterization of the fast sodium current in isolated rat myocardial cells: Simulation of the clamped membrane potential. J. Physiol. (London) 325:301–315.Google Scholar
  48. 48.
    Bustamante, J. O., and T. F. McDonald. 1983. Sodium currents in segments of human heart cells. Science 220:320–321.PubMedGoogle Scholar
  49. 49.
    Cachelin, A. B., J. E. DePeyer, S. Kokubun, and H. Reuter. 1983. Sodium channels in cultured cardiac cells. J. Physiol. (London) 340:389–401.Google Scholar
  50. 50.
    Hamill, O. P., A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth. 1981. Improved patch clamp techniques for high resolution patch clamp recording from cells and cell-free membrane patches. Pfluegers Arch. 391:85–100.Google Scholar
  51. 51.
    Myerburg, R. J., H. Gelband, and B. F. Hoffman. 1971. Functional characteristics of the gating mechanism in the canine A-V conducting system. Circ. Res. 28:136–147.PubMedGoogle Scholar
  52. 52.
    Singer, D. H., R. Lazzara, and B. F. Hoffman. 1967. Interrelationships between automaticity and conduction in Purkinje fibers. Circ. Res. 21:537–558.PubMedGoogle Scholar
  53. 53.
    Singh, B. N., and E. M. Vaughan-Williams. 1971. Effect of altering potassium concentration on the action of lidocaine and diphenylhydantoin on rabbit atrial and ventricular muscle. Circ. Res. 29:286–295.PubMedGoogle Scholar
  54. 54.
    Hondeghem, L. M., and B. G. Katzung. 1977. Time-and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim. Biophys. Acta 472:373–398.PubMedGoogle Scholar
  55. 55.
    Hille, B. 1977. Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction. J. Gen. Physiol. 69:497–515.PubMedGoogle Scholar
  56. 56.
    Bean, B. P., C. J. Cohen, and R. W. Tsien. 1983. Lidocaine block of cardiac sodium channels. J. Gen. Physiol. 81:613–642.PubMedGoogle Scholar
  57. 57.
    Weidmann, S. 1955. Effects of calcium ions and local anesthetics on the electrical properties of Purkinje fibres. J. Physiol. (London) 129:568–582.Google Scholar
  58. 58.
    Hagiwara, S., and S. Nakajima. 1966. Differences in Na and Ca spikes as examined by application of tetrodotoxin, procaine and manganese ions. J. Gen. Physiol. 49:793–806.PubMedGoogle Scholar
  59. 59.
    Reuter, H., C. F. Stevens, R. W. Tsien, and G. Yellen. 1982. Properties of single calcium channels in cardiac cell culture. Nature (London) 297:501–504.Google Scholar
  60. 60.
    Cavalie, A., R. Ochi, D. Pelzer, and W. Trautwein. 1983. Elementary currents through Ca channels in guinea pig myocytes. Pfluegers Arch. 398:284–297.Google Scholar
  61. 61.
    Eckert, R., D. L. Tillotson, and P. Brehm. 1981. Calcium mediated control of Ca and K currents. Fed. Proc. 40:2226–2232.PubMedGoogle Scholar
  62. 62.
    Marban, E., and R. W. Tsien. 1982. Enhancement of calcium current during digitalis inotropy in mammalian heart: Positive feedback regulation by intracellular calcium. J. Phvsiol. (London) 329:589–614.Google Scholar
  63. 63.
    Tsien, R. W. 1983. Calcium channels in excitable cell membranes. Annu. Rev. Physiol. 45:341–358.PubMedGoogle Scholar
  64. 64.
    Mentrard, D., G. Vassort, and R. Fischmeister. 1984. Calcium mediated inactivation of the calcium conductance in cesium loaded frog heart cells. J. Gen. Physiol. 83:105–131.PubMedGoogle Scholar
  65. 65.
    Lee, K. S., and R. W. Tsien. 1982. Reversal of current through calcium channels in dialysed single heart cells. Nature (London) 297:498–501.Google Scholar
  66. 66.
    Sigworth, F. J. 1980. The variance of sodium current fluctuations at the node of Ranvier. J. Physiol. (London) 307:97–129.Google Scholar
  67. 67.
    Janis, R. A., and D. J. Triggle. 1983. New developments in Ca channel antagonists. J. Med. Chem. 26:775–785.PubMedGoogle Scholar
  68. 68.
    Reuter, H., and H. Scholz. 1977. A study of the ion selectivity and the kinetic properties of the calcium dependent slow inward current in mammalian cardiac muscle. J. Phvsiol. (London) 264:17–47.Google Scholar
  69. 69.
    Lee, K. S., and R. W. Tsien. 1984. High selectivity of calcium channels in single dialyzed heart cells of the guinea pig. J. Physiol (London) 354:253–272.Google Scholar
  70. 70.
    Hagiwara, S., J. Fukuda, and D. C. Eaton. 1974. Membrane currents carried by Ca, Sr, and Ba in barnacle muscle fiber during voltage clamp. J. Gen. Physiol. 63:564–578.PubMedGoogle Scholar
  71. 71.
    Vereecke, J., and E. E. Carmeliet. 1971. Sr action potentials in cardiac Purkinje fibers. II. Dependence of the Sr conductance on the external Sr concentration and Sr-Ca antagonism. Pfluegers Arch. 322:73–82.Google Scholar
  72. 72.
    Hess, P., and R. W. Tsien. 1984. Mechanism of ion permeation through calcium channels. Nature (London) 309:453–456.Google Scholar
  73. 73.
    Lee, K. S., and R. W. Tsien. 1983. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialyzed heart cells. Nature (London) 302:790–794.Google Scholar
  74. 74.
    Cavalie, A., Pelzer, D., and W. Trautwein. 1985. Modulation of the gating properties of single calcium channels by D600 in guinea pig ventricular myocytes. J. Physiol. (London) 358:59.Google Scholar
  75. 75.
    Schramm, M., G. Thomas, R. Towart, and G. Franckowiak. 1983. Novel dihydropyridines with positive inotropic action through activation of Ca channels. Nature (London) 303:535–537.Google Scholar
  76. 76.
    Katzung, B. G., L. M. Hondeghem, and A. O. Grant. 1975. Cardiac ventricular automaticity induced by current of injury. Pfluegers Arch. 360:193–197.Google Scholar
  77. 77.
    Chapman, R. 1979. Excitation-contraction coupling in cardiac muscle. Prog. Biophys. Mol. Biol. 35:1–52.PubMedGoogle Scholar
  78. 78.
    Fabiato, A. 1983. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am. J. Physiol. 245:C1–C14.PubMedGoogle Scholar
  79. 79.
    Eisner, D. A., and R. D. Vaughan-Jones. 1983. Do calcium-activated potassium channels exist in the heart? Cell Calcium 4:371–386.PubMedGoogle Scholar
  80. 80.
    Reuter, H. 1984. Ion channels in cardiac cell membranes. Annu. Rev. Physiol. 46:473–484.PubMedGoogle Scholar
  81. 81.
    Noble, D. 1979. The Initiation of the Heartbeat. Oxford University Press, London.Google Scholar
  82. 82.
    Adrian, R. H. 1969. Rectification in muscle membrane. Prog. Biophys. Mol. Biol. 19:339–369.PubMedGoogle Scholar
  83. 83.
    Hille, B., and W. Schwarz. 1978. Potassium channels as multi-ion single-file pores. J. Gen. Physiol. 72:409–441.PubMedGoogle Scholar
  84. 84.
    Sakmann, B., and G. Trube. 1984. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J. Physiol. (London) 347:641–657.Google Scholar
  85. 85.
    Noble, D., and R. W. Tsien. 1969. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. J. Physiol. (London) 200:205–231.Google Scholar
  86. 86.
    McDonald, T. F., and W. Trautwein. 1978. The potassium current underlying delayed rectification in cat ventricular muscle. J. Physiol. (London) 274:193–216.Google Scholar
  87. 87.
    Brown, H., and DiFrancesco, D. 1980. Voltage-clamp investigations of membrane currents underlying pace-maker activity in rabbit sino-atrial node. J. Physiol. (London) 308:331–351.Google Scholar
  88. 88.
    Kass, R. S., and R. W. Tsien. 1975. Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J. Gen. Physiol. 66:169–192.PubMedGoogle Scholar
  89. 89.
    Kass, R. S. 1982. Delayed rectification is not a calcium activated current in cardiac Purkinje fibers. Biophys. J. 37:342a.Google Scholar
  90. 90.
    Clapham, D. E., and L. J. DeFelice. 1984. Voltage-activated K channels in embryonic heart. Biophys. J. 45:40–42.PubMedGoogle Scholar
  91. 91.
    Coronado, R., and R. Latorre. 1982. Detection of K+ and Cl channels from calf cardiac sarcolernma in planar lipid bilayer membranes. Nature (London) 298:849–852.Google Scholar
  92. 92.
    Dudel, J., K. Peper, R. Rudel, and W. Trautwein. 1967. The dynamic chloride component of membrane current in Purkinje fibres. Pfluegers Arch. 295:197–212.Google Scholar
  93. 93.
    Kenyon, J. L., and W. R. Gibbons. 1979. 4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers. J. Gen. Physiol. 73:139–157.PubMedGoogle Scholar
  94. 94.
    DiFrancesco, D., and P. A. McNaughton. 1979. The effects of calcium on outward membrane currents in the cardiac Purkinje fibre. J. Physiol. (London) 289:347–373.Google Scholar
  95. 95.
    Siegelbaum, S. A., and R. W. Tsien. 1980. Calcium-activated transient outward current in calf cardiac Purkinje fibres. J. Physiol. (London) 299:485–506.Google Scholar
  96. 96.
    Coraboeuf, E., and E. Carmeliet. 1982. Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pfluegers Arch. 392:352–359.Google Scholar
  97. 97.
    Josephson, I., and J. Sanchez-Chapula. 1982. Plateau membrane currents in single heart cells. Biophys. J. 37:238a.Google Scholar
  98. 98.
    Ito, K., J. L. Kenyon, G. Isenberg, and J. L. Sutko. 1984. The existence of two components of transient outward current in isolated cardiac ventricular myocytes. Biophys. J. 45:54a.Google Scholar
  99. 99.
    Marban, E., and R. W. Tsien. 1982. Effects of nystatin-mediated intracellular ion substitution on membrane currents in calf Purkinje fibres. J. Physiol. (London) 329:569–587.Google Scholar
  100. 100.
    Kass, R. S., T. Scheuer, and K. J. Malloy. 1982. Block of outward current in cardiac Purkinje fibers by injection of quaternary ammonium ions. J. Gen. Physiol. 79:1041–1063.PubMedGoogle Scholar
  101. 101.
    Vereecke, J., G. Isenberg, and E. Carmeliet. 1980. K efflux through inward rectifying K channels in voltage clamped Purkinje fibers. Pfluegers Arch. 384:207–217.Google Scholar
  102. 102.
    Wier, W. G. 1980. Calcium transients during excitation-contraction coupling in mammalian heart: Aequorin signals of canine Purkinje fibers. Science 207:1085–1087.PubMedGoogle Scholar
  103. 103.
    Noma, A. 1983. ATP-regulated K+ channels in cardiac muscle. Nature (London) 305:147–148.Google Scholar
  104. 104.
    Yanagihira, K., and H. Irisawa. 1980. Inward current activated during hyperpolarization in the rabbit sinoatrial node cell. Pfluegers Arch. 385:11–19.Google Scholar
  105. 105.
    DiFrancesco, D. 1981. A new interpretation of the pace-maker current in calf Purkinje fibres. J. Physiol. (London) 314:359–376.Google Scholar
  106. 106.
    Maylie, J., M. Morad, and J. Weiss. 1981. A study of pace-maker potential in rabbit sino-atrial node: Measurement of potassium activity under voltage clamp condition. J. Physiol. (London) 311:161–178.Google Scholar
  107. 107.
    Kokubun, S., M. Nishimura, A. Noma, and H. Irisawa. 1982. Membrane currents in the rabbit atrioventricular node cell. Pfluegers Arch. 393:15–22.Google Scholar
  108. 108.
    Cohen, I. S., R. T. Falk, and N. K. Mulrine. 1983. Actions of barium and rubidium on membrane currents in canine Purkinje fibers. J. Physiol. (London) 338:589–612.Google Scholar
  109. 109a.
    DiFrancesco, D. 1981. A study of the ionic nature of the pacemaker current in calf Purkinje fibres. J. Physiol. (London) 314:377–393.Google Scholar
  110. 109b.
    Noble, D. 1984. The surprising heart. A review of recent progress in cardiac electrophysiology. J. Physiol. (London) 353:1–50.Google Scholar
  111. 110.
    Noma, A., H. Kotake, and H. Irisawa. 1980. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node. Pfluegers Arch. 388:1–9.Google Scholar
  112. 111.
    Brown, H. F. 1982. Electrophysiology of the sinoatrial node. Physiol. Rev. 62:505–530.PubMedGoogle Scholar
  113. 112.
    Yanagihira, K., and H. Irisawa. 1980. Potassium current during the pacemaker depolarization in rabbit sino-atrial node cells. Pfluegers Arch. 388:255–260.Google Scholar
  114. 113.
    Noma, A., M. Morad, and H. Irisawa. 1983. Does the “pacemaker current” generate the diastolic depolarization in the rabbit SA node cells? Pfluegers Arch. 397:190–194.Google Scholar
  115. 114.
    Ferner, G. R. 1977. Digitalis arrhythmias: Role of oscillatory after-potentials. Prog. Cardiovasc. Dis. 19:459–474.Google Scholar
  116. 115.
    Lederer, W. J., and R. W. Tsien. 1976. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J. Physiol. (London) 263:73–100.Google Scholar
  117. 116.
    Karagueuzian, H. S., and B. G. Katzung. 1982. Voltage-clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle. J. Physiol. (London) 332.255–571.Google Scholar
  118. 117.
    Matsuda, H., A. Noma, Y. Kurachi, and H. Irisawa. 1982. Transient depolarization and spontaneous voltage fluctuations in isolated single cells from guinea pig ventricles: Calcium-mediated membrane potential fluctuations. Circ. Res. 51:142–151.PubMedGoogle Scholar
  119. 118.
    Kass, R. S., W. J. Lederer, R. W. Tsien, and R. Weingart. 1978. Role of calcium ions in transient inward currents and aftercontrac-tions induced by strophanthidin in cardiac Purkinje fibres. J. Physiol. (London) 281:187–208.Google Scholar
  120. 119.
    Kass, R. S., R. W. Tsien, and R. Weingart. 1978. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J. Physiol. (London) 281:209–226.Google Scholar
  121. 120.
    Colquhoun, D., E. Neher, H. Reuter, and C. F. Stevens, 1981. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature (London) 294:752–754.Google Scholar
  122. 121.
    Eisner, D., W. J. Lederer, and S. S. Sheu. 1983. The role of intracellular sodium activity in the anti-arrhythmic action of local anaesthetics in sheep Purkinje fibres. J. Physiol. (London) 340:239–257.Google Scholar
  123. 122.
    Wier, W. G., and P. Hess. 1984. Excitation-contraction coupling in cardiac Purkinje fibers: Effects of cardiotonic steroids on the intracellular [Ca2+ ] transient, membrane potential, and contraction. J. Gen. Physiol. 83:395–415.PubMedGoogle Scholar
  124. 123.
    Orchard, C. H., D. A. Eisner, and D. G. Allen. 1983. Oscillations of intracellular Ca2+ in mammalian cardiac muscle. Nature (London) 304:735–738.Google Scholar
  125. 124.
    Kehoe, J., and A. Marty. 1980. Certain slow post-synaptic responses: Their properties and possible underlying mechanisms. Annu. Rev. Biophys. Bioeng. 9:437–465.PubMedGoogle Scholar
  126. 125.
    Hartzell, H. C. 1981. Mechanisms of slow post-synaptic potentials. Nature (London) 291:539–544.Google Scholar
  127. 126.
    Reuter, H. 1983. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature (London) 301:569–574.Google Scholar
  128. 127.
    Siegelbaum, S. A., and R. W. Tsien. 1984. Modulation of gated ion channels as a mode of transmitter action. Trends Neurosci. 6:307–313.Google Scholar
  129. 128.
    Tsien, R. W. 1977. Cyclic AMP and contractile activity in the heart. Adv. Cyclic Nucleotide Res. 8:363–420.PubMedGoogle Scholar
  130. 129.
    Katz, A. M. 1983. Cyclic adenosine monophosphate effects on the myocardium: A man who blows hot and cold with one breath. J. Am. Coll. Cardiol. 2:143–149.PubMedGoogle Scholar
  131. 130.
    Costa, M. R. C., J. E. Casnellie, and W. A. Catterall. 1982. Selective phosphorylation of the α subunit of the sodium channel by cAMP-dependent protein kinase. J. Biol. Chem. 257:7918–7921.PubMedGoogle Scholar
  132. 131.
    Vassort, G., O. Rougier, D. Gamier, M. P. Sauviat, E. Coraboeuf, and Y. M. Gargouil. 1969. Effects of adrenaline on membrane inward currents during the cardiac action potential. Pfluegers Arch. 309:70–81.Google Scholar
  133. 132.
    Reuter, H., and H. Scholz. 1977. The regulation of the Ca conductance of cardiac muscle by adrenaline. J. Physiol. (London) 264:49–62.Google Scholar
  134. 133.
    Bean, B. P., M. C. Nowycky, and R. W. Tsien. 1984. ß-Adre-nergic modulation of calcium channels in frog ventricular heart cells. Nature (London) 307:371–375.Google Scholar
  135. 134.
    Tsien, R. W. 1973. Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibers. Nature New Biol. 245:120–122.PubMedGoogle Scholar
  136. 135.
    Yamasaki, Y., M. Fujiwara, and N. Toda. 1974. Effects of intra-cellularly applied cyclic 3′, 5′-adenosine monophosphate and di-butyryl cyclic 3′, 5′-adenosine monophosphate on the electrical activity of sinoatrial nodal cells of the rabbit. J. Pharmacol. Exp. Ther. 190:15–20.PubMedGoogle Scholar
  137. 136.
    Vogel, S., and N. Sperelakis. 1981. Induction of slow action potentials by microiontophoresis of cyclic AMP into heart cells. J. Mol. Cell. Cardiol. 13:51–64.PubMedGoogle Scholar
  138. 137.
    Tsien, R. W., W. R. Giles, and P. Greengard. 1972. Cyclic AMP mediates the action of adrenaline on the action potential plateau of cardiac Purkinje fibres. Nature New Biol. 240:181–183.PubMedGoogle Scholar
  139. 138.
    Reuter, H. 1974. Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J. Physiol. (London) 242:429–451.Google Scholar
  140. 139.
    Li, T., and N. Sperelakis. 1983. Stimulation of slow action potentials in guinea pig papillary muscle cells by intracellular injection of cAMP, Gpp(NH)p, and cholera toxin. Circ. Res. 52:111–117.PubMedGoogle Scholar
  141. 140.
    Osterrieder, W., G. Brum, J. Hescheler, W. Trautwein, V. Flockerzi, and F. Hofmann. 1982. Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature (London) 298:576–578.Google Scholar
  142. 141.
    Cachelin, A.B., J.E. de Peyer, S. Kokubun, and H. Reuter. 1983. Calcium channel modulation by 8-bromo-cyclic AMP in cultured heart cells. Nature (London) 304:462–464.Google Scholar
  143. 142.
    Brum, G., W. Osterrieder, and W. Trautwein. 1984. β-Adre-nergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pfluegers Arch. 401:111–118.Google Scholar
  144. 143.
    Otsuka, M. 1958. Die Wirkung von Adrenalin auf Purkinje-Fasern von Säugetieren. Pfluegers Arch. Gesamte Physiol. 266:512–517.Google Scholar
  145. 144.
    Hauswirth, O., D. Noble, and R. W. Tsien. 1968. Adrenaline: Mechanism of action of the pacemaker potential in cardiac Purkinje fibres. Science 162:916–917.PubMedGoogle Scholar
  146. 145.
    Tsien, R. W. 1974. Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J. Gen. Physiol. 64:293–319.PubMedGoogle Scholar
  147. 146.
    Brown, H., D. DiFrancesco, and S. J. Noble. 1979. How does adrenaline accelerate the heart? Nature (London) 280:235–236.Google Scholar
  148. 147.
    Tsien, R. W. 1974. Mode of action of chronotropic agents in cardiac Purkinje fibers: Does epinephrine act by directly modifying the external surface charge? J. Gen. Physiol. 64:320–342.PubMedGoogle Scholar
  149. 148.
    Brown, H. F., P. A. McNaughton, D. Noble, and S. J. Noble. 1975. Adrenergic control of cardiac pacemaker currents. Philos. Trans. R. Soc. London Ser. B 270:527–537.Google Scholar
  150. 149.
    Pappano, A. J., and E. Carmeliet. 1979. Epinephrine and the pacemaker mechanism at plateau potentials in sheep cardiac Purkinje fibers. Pfluegers Arch. 382:17–26.Google Scholar
  151. 150.
    Kass, R. S., and S. E. Wiegers. 1982. The ionic basis of concentration-related effects of noradrenaline on the action potential of calf cardiac Purkinje fibres. J. Physiol. (London) 322:541–558.Google Scholar
  152. 151.
    Scholz, H., and H. Reuter. 1976. Effect of theophylline on membrane currents in mammalian cardiac muscle. Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 293:R19.Google Scholar
  153. 152.
    Gadsby, D. 1984. β-adrenoceptor agonists increase membrane K+ conductance in cardiac Purkinje fibres. Nature (London) 306:691–693.Google Scholar
  154. 153.
    Hutter, O. F. 1957. Mode of action of autonomic transmitters on the heart. Br. Med. Bull. 13:176–180.PubMedGoogle Scholar
  155. 154.
    Trautwein, W., and J. Dudel. 1958. Zum Mechanismus der Membranwirkung des Acetylcholins an der Herzmuskelfaser. Pfluegers Arch. 266:324–334.Google Scholar
  156. 155.
    Woodbury, W. W., and W. E. Crill. 1961. On the problems of impulse conduction in the atrium. In: Nervous Inhibition. E. Florey, ed. Pergamon Press, Elmsford, N.Y. pp. 124–134.Google Scholar
  157. 156.
    Giles, W., and S. J. Noble. 1976. Changes in membrane current in bullfrog atrium produced by acetylcholine. J. Physiol. (London) 261:103–123.Google Scholar
  158. 157.
    Garnier, D., J. Nargeot, C. Ojeda, and O. Rougier. 1978. The action of acetylcholine on background conductance in frog atrial trabeculae. J. Physiol. (London) 274:381–396.Google Scholar
  159. 158.
    Ojeda, C., O. Rougier, and Y. Tourneur. 1981. Effects of Cs on acetylcholine induced current: Is iK increased by acetylcholine in frog atrium? Pfluegers Arch. 391:57–59.Google Scholar
  160. 159.
    Sakmann, B., A. Noma, and W. Trautwein. 1983. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature (London) 303:250–253.Google Scholar
  161. 160.
    Mirro, M. J., J. C. Bailey, and A. M. Watanabe. 1979. Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria. Circ. Res. 45:225–233.PubMedGoogle Scholar
  162. 161.
    Fleming, B. P., W. Giles, and W. J. Lederer. 1981. Are acetyl-choline-induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pacemaker tissue? J. Physiol. (London) 314:47–64.Google Scholar
  163. 162.
    Trautwein, W., J. Taniguchi, and A. Noma. 1982. The effect of intracellular cyclic nucleotides and calcium and the action potential and acetylcholine response of isolated cardiac cells. Pfluegers Arch. 392:307–314.Google Scholar
  164. 163.
    Soejima, M., and A. Noma. 1983. The K channel coupled with the muscarinic ACh receptor in the heart muscle. Proc. Int. Union Physiol. Sci. 15:51.Google Scholar
  165. 164.
    Giles, W., and R. W. Tsien. 1975. Effects of acetylcholine on membrane currents in frog atrial muscle. J. Physiol. (London) 246:64P-66P.Google Scholar
  166. 165.
    Ikemoto, Y., and M. Goto. 1975. Nature of the negative inotropic effect of acetylcholine on the myocardium. Proc. Jpn. Acad. 51:501–505.Google Scholar
  167. 166.
    Levy, M. N. 1977. Parasympathetic control of the heart. In: Neural Regulation of the heart. W. C. Randall, ed. Oxford University Press, London, pp. 95–129.Google Scholar
  168. 167.
    Giles, W., and S. J. Noble. 1976. Changes in membrane currents in bullfrog atrium produced by acetylcholine. J. Physiol. (London) 261:103–123.Google Scholar
  169. 168.
    Ten Eick, R., H. Nawrath, T. F. McDonald, and W. Trautwein. 1976. On the mechanism of the negative inotropic effect of acetylcholine. Pfluegers Arch. 361:207–213.Google Scholar
  170. 169.
    Hino, N., and R. Ochi. 1980. Effect of acetylcholine on membrane currents in guinea-pig papillary muscle. J. Physiol. (London) 307:183–197.Google Scholar
  171. 170.
    Biegon, R. L., and A. J. Pappano. 1980. Dual mechanism for inhibition of calcium-dependent action potentials by acetylcholine in avian ventricular muscle. Circ. Res. 46:353–362.PubMedGoogle Scholar
  172. 171.
    Josephson, I., and N. Sperelakis. 1982. On the ionic mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle. J. Gen. Physiol. 79:69–86.PubMedGoogle Scholar
  173. 172.
    Gamier, D., J. Nargeot, C. Ojeda, and O. Rougier. 1978. Action of carbachol on atrial fibres: Induced extra current and slow inward current inhibition. J. Physiol. (London) 276:27P-28P.Google Scholar
  174. 173.
    Inoue, D., M. Hachisu, and A. J. Pappano. 1983. Acetylcholine increases resting membrane potassium conductance in atrial but not in ventricular muscle during muscarinic inhibition of Ca++-dependent action potentials in chick heart. Circ. Res. 53:158–167.PubMedGoogle Scholar
  175. 174.
    Inui, J., and H. Imamura. 1977. Effects of acetylcholine on calcium-dependent electrical and mechanical responses in the guinea-pig papillary muscle partially depolarized by potassium. Naunyn-Schmiedeberg’s Arch. Pharmacol. 299:1–7.Google Scholar
  176. 175.
    Biegon, R. L., P. M. Epstein, and A. J. Pappano. 1980. Muscarinic antagonism of the effects of a phosphodiesterase inhibitor (methylisobutylxanthine) in embryonic chick ventricle. J. Pharmacol. Exp. Ther. 215:348–356.PubMedGoogle Scholar
  177. 176.
    Linden, J., S. Vogel, and N. Sperelakis. 1982. Sensitivity of Ca-dependent slow action potentials to methacholine is induced by phosphodiesterase inhibitors in embryonic chick ventricles. J. Pharmacol. Exp. Ther. 222:383–387.PubMedGoogle Scholar
  178. 177.
    Nawrath, H. 1977. Does cyclic GMP mediate the negative inotropic effect of acetylcholine in the heart? Nature (London) 267:72–74.Google Scholar
  179. 178.
    Kohlhardt, M., and K. Haap. 1978. 8-Bromo-guanosine-3′, 5′-monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium. J. Mol. Cell. Cardiol. 10:573–586.PubMedGoogle Scholar
  180. 179.
    Ikemoto, Y., and M. Goto. 1976. Effects of acetylcholine and cyclic nucleotides on the bullfrog atrial muscle. Recent Adv. Stud. Card. Struct. Metab. 11:57–61.Google Scholar
  181. 180.
    Watanabe, A. M., M. M. McConnaughey, R. A. Strawbridge, J. W. Fleming, and H. R. Besch. 1978. Muscarinic cholinergic receptor antagonism of β-adrenergic receptor affinity for catecholamines. J. Biol. Chem. 253:4833–4836.PubMedGoogle Scholar
  182. 181.
    Weidmann, S. 1966. Cardiac electrophysiology in the light of recent morphological findings. Harvey Lect. 61:1–15.Google Scholar
  183. 182.
    McNutt, N. S., and D. W. Fawcett. 1974. Myocardial ultrastructure. In: The Mammalian Myocardium. G. A. Langer and A. J. Brady, eds. Wiley, New York.Google Scholar
  184. 183.
    Netter, F. H. 1969. The CIBA Collection of Medical Illustrations, Volume 5. Elsevier, Amsterdam.Google Scholar
  185. 184.
    Weidmann, S. 1957. Resting and action potentials of cardiac muscle. Ann. N.Y. Acad. Sci. 65:663–678.PubMedGoogle Scholar
  186. 185.
    Dudel, J., K. Peper, R. Rudel, and W. Trautwein. 1967. The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pfluegers Arch. 295:213–226.Google Scholar
  187. 186.
    Kass, R. S., and R. W. Tsien. 1975. Multiple effects of calcium antagonists in cardiac Purkinje fibers. J. Gen. Physiol. 66:169–192.PubMedGoogle Scholar
  188. 187.
    Hutter, O. F., and W. Trautwein. 1956. Vagal and sympathetic effects on the pacemaker fibres in the sinus venosus of the heart. J. Gen. Physiol. 39:715–733.PubMedGoogle Scholar
  189. 188.
    Toda, N., and T. C. West. 1967. Interactions of K, Na, and vagal stimulation in the S-A node of the rabbit. Am. J. Physiol. 212:416–423.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Richard W. Tsien
    • 1
  • Peter Hess
    • 1
  1. 1.Department of PhysiologyYale University School of MedicineNew HavenUSA

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