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Electrophysiological effects of cardiac glycosides

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Cardiac Glycosides 1785–1985

Summary

In this paper we review the effects of cardiac glycosides on the electrophysiological properties of mammalian cardiac muscle. Cardiac glycosides produce an initial prolongation of the action potential due to inhibition of the electrogenic Na-K pump current. This is then followed by a gradual decrease of action potential duration to less than control length. The origin of this decrease is uncertain. Cardiac glycosides also produce a transient depolarization which follows the action potential and which can produce a spontaneous action potential. This transient depolarization is produced by a transient inward current which results from a Ca-activated conductance. The triggering increase of [Ca2+]i originates from the spontaneous release of Ca ions from the sarcoplasmic reticulum (s. r.). Both this spontaneous release and the resulting transient inward current can be abolished by inhibitors of s. r. function such as caffeine and ryanodine. As well as these oscillations of [Ca2+]i which follow repolarization, there are also spontaneous oscillations in the absence of stimulation. These spontaneous oscillations, which also result from release of Ca from the sarcoplasmic reticulum, interfere with the systolic rise of Ca produced by stimulation. Thus the Ca oscillations are not only responsible for the cardiac arrhythmias produced by digitalis but also compromise the magnitude of the positive inotropic effect.

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References

  1. Allen DG, Blinks JR (1978) Calcium transients in aequorin-injected frog cardiac muscle. Nature, London 273: 509–513

    Article  CAS  Google Scholar 

  2. Allen DG, Eisner DA, Pirolo JS, Smith GL (1985) The relationship between intracellular calcium and contraction in calcium-overloaded ferret papillary muscles. J Physiol 364: 169–182

    PubMed  CAS  Google Scholar 

  3. Arlock P, Katzung BG (1985) Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle. J Physiol 360: 105–120

    PubMed  CAS  Google Scholar 

  4. Berlin JR, Cannel MB, Goldman WF, Lederer WJ, Marban E, Wier WG (1986) Subcellular calcium inhomogeneity indicated by fura-2 develops with calcium-overload in single rat heart cells. J Physiol 371: 200 p.

    Google Scholar 

  5. Cannell MB, Lederer WJ (1986) The arrhythmogenic inward current ITI in the absence of electrogenic sodium-calcium exchange in sheep cardiac Purkinje fibres. J Physiol (in press)

    Google Scholar 

  6. Colquhoun D, Neher E, Reuter H, Stevens CF (1981) Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature, London 294: 752–754

    Article  CAS  Google Scholar 

  7. DiPolo RH, Rojas H, Beauge L (1982) Ca entry at rest and during prolonged depolarization in dialyzed squid axons. Cell Calcium 3: 19–41

    Article  PubMed  CAS  Google Scholar 

  8. Eisner DA, Lederer WJ (1985) Na-Ca exchange: stoichiometry and electrogenicity. Am J Physiol 248: C189–202

    PubMed  CAS  Google Scholar 

  9. Eisner DA, Orchard CH, Allen DG (1984) Control of intracellular ionized calcium concentration by sarcolemmal and intracellular mechanisms. J mol cell Cardiol 16: 137–146

    Article  PubMed  CAS  Google Scholar 

  10. Eisner DA, Valdeolmillos M (1985) The mechanism of the increase of tonic tension produced by caffeine in sheep cardiac Purkinje fibres. J Physiol 364: 313–326

    PubMed  CAS  Google Scholar 

  11. Eisner DA, Valdeolmillos M (1986) A study of intracellular calcium oscillations in sheep cardiac Purkinje fibres measured at the single cell level. J Physiol 372: 539–556

    PubMed  CAS  Google Scholar 

  12. Eisner DA, Vaughan-Jones RD (1983) Do calcium-activated potassium channels exist in the heart? Cell Calcium 4: 371–386

    Article  PubMed  CAS  Google Scholar 

  13. Fabiato A, Fabiato F (1975) Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. J Physiol 249: 469–495

    PubMed  CAS  Google Scholar 

  14. Fabiato A (1985) Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J gen Physiol 85: 247–289

    Article  PubMed  CAS  Google Scholar 

  15. Fedida D, Noble D, Spindler AJ (1985) Simultaneous recording of transient inward current and attraction in single guinea-pig ventricular cells. J Physiol 366: 119 p.

    Google Scholar 

  16. Ferrier GR, Saunders JH, Mendez C (1973) A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circulation Res 33: 508–515

    Article  PubMed  CAS  Google Scholar 

  17. Glitsch HG, Pott L (1975) Spontaneous tension oscillations in guinea-pig atrial trabecuale. Pflugers Arch 358: 11–25

    Article  PubMed  CAS  Google Scholar 

  18. Isenberg G (1975) Is potassium conductance of cardiac Purkinje fibres controlled by [Ca21? Nature 253: 273–274

    Article  CAS  Google Scholar 

  19. Isenberg G, Trautwein W (1974) The effect of dihydro-ouabain and lithium ions on the outward current in cardiac Purkinje fibres. Pflugers Arch 350: 41–54

    Article  PubMed  CAS  Google Scholar 

  20. Kakei M, Noma A, Shibasaki T (1985) Properties of adenosinetriphosphate-regulated potassium-channels in guinea-pig ventricular cells. J Physiol 363: 441–462

    PubMed  CAS  Google Scholar 

  21. Kameyama M, Kakei M, Sato R, Shibasaki T, Matsuda H, Irisawa H (1984) Intracellular Na’ activates a K+ channel in mammalian cardiac cells. Nature 309: 354–356

    Article  PubMed  CAS  Google Scholar 

  22. Karagueuzian HS, Katzung BG (1982) Voltage-clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle. J Physiol 327: 255–271

    PubMed  CAS  Google Scholar 

  23. Kass RS, Lederer WJ, Tsien RW, Weingart E (1978a) Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol 281: 187–208

    PubMed  CAS  Google Scholar 

  24. Kass RS, Tsien RW (1982) Fluctuations in membrane current driven by intracellular calcium in cardiac Purkinje fibres. Biophys Journal 38: 259–269

    Article  CAS  Google Scholar 

  25. Kass RS, Tsien RW, Weingart R (1978b) Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol 281: 209–226

    PubMed  CAS  Google Scholar 

  26. Lederer WJ (1976) The ionic basis of arrhythmogenic effects of cardiotonic steroids in canine Purkinje fibres. Ph D. Dissertation Physiology Department: Yale University, New Haven, CT

    Google Scholar 

  27. Lederer WJ, Tsien RW (1976) Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol 263: 73–100

    PubMed  CAS  Google Scholar 

  28. Matsuda H (1983) Effects of intracellular calcium injection on steady-state membrane currents in isolated single ventricular cells. Pflugers Arch 397: 81–83

    Article  PubMed  CAS  Google Scholar 

  29. Matsuda H, Noma A, Kurachi Y, Irisawa H (1982) Transient depolarization and spontaneous voltage fluctuations in isolated single cells from guinea-pig ventricles. Calcium mediated membrane potential fluctuations. Circulation Res 51: 142–151

    Article  PubMed  CAS  Google Scholar 

  30. Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305: 147–148

    Article  PubMed  CAS  Google Scholar 

  31. Orchard CH, Eisner DA, Allen DG (1983) Oscillations of intracellular Cat+ in mammalian cardiac muscle. Nature 304: 735–738

    Article  PubMed  CAS  Google Scholar 

  32. Rosen MR, Gelband H, Hoffman BF (1973) Correlation between effects of ouabain on the canine electrocardiogram and transmembrane potentials in isolated Purkinje fibres. Circulation 47: 65–72

    Article  PubMed  CAS  Google Scholar 

  33. Valdeolmillos M, Eisner DA (1985) The effects of ryanodine on calcium-overloaded sheep cardiac Purkinje fibres. Circ Res 56: 452–456

    Article  PubMed  CAS  Google Scholar 

  34. Vassalle M, Lin CI (1979) Effect of calcium on strophanthidin-induced electrical and mechanical toxicity in cardiac Purkinje fibres. Am J Physiol 236: H689–697

    PubMed  CAS  Google Scholar 

  35. Wier WG, Kort AA, Stern MD, Lakatta EG, Marban E (1983) Cellular calcium fluctuations in mammalian heart: direct evidence from noise analysis of aequorin signals in Purkinje fibres. Proceedings of the National Academy of Sciences USA 80: 7367–7371

    Article  CAS  Google Scholar 

  36. Wollenberger A (1949) The energy metabolism of the failing heart and the metabolic action of the cardiac glycosides. Pharmacol Rev 1: 311–352

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physiology, University College London, Gower Street, London, WC lE 6BT, England

    Dr. D. A. Eisner

  2. Department of Physiology, University College London, England

    M. Valdeolmillos

  3. Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    W. J. Lederer & M. B. Cannell

Authors
  1. Dr. D. A. Eisner
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  2. M. Valdeolmillos
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  3. W. J. Lederer
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  4. M. B. Cannell
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Editor information

Editors and Affiliations

  1. Medizinische Klinik I, Klinikum Großhadern der Universität München, Marchioninistraße 15, 8000, München 70, West Germany

    Erland Erdmann

  2. Institut für Pharmakologie, Universität Düsseldorf, Moorenstraße 5, 4000, Düsseldorf, West Germany

    K. Greef

  3. Biophysik Institut, Aarhus Universitet, Universitetparken, 8000, Aarhus, Denmark

    J. C. Skou

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© 1986 Springer-Verlag Berlin Heidelberg

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Eisner, D.A., Valdeolmillos, M., Lederer, W.J., Cannell, M.B. (1986). Electrophysiological effects of cardiac glycosides. In: Erdmann, E., Greef, K., Skou, J.C. (eds) Cardiac Glycosides 1785–1985. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11292-2_11

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  • DOI: https://doi.org/10.1007/978-3-662-11292-2_11

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-662-11294-6

  • Online ISBN: 978-3-662-11292-2

  • eBook Packages: Springer Book Archive

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