The use of isolated mammalian cardiac myocytes for the study of inotropic mechanisms

  • M. R. Mitchell
  • T. Powell
  • D. A. Terrar
  • V. W. Twist


The complex structure of cardiac muscle, in which adjacent cells are electrically coupled, is necessary to allow conduction of the action potential through the organ to initiate contraction in a controlled manner, but this complexity presents difficulties for the study of how electrical activity is coupled to contraction. The use of single myocytes isolated from their neighbours greatly simplifies the analysis of electrical activity in cardiac muscle, since the problems arising from the restricted extracellular spaces and from the syncitial nature of multicellular preparations are reduced or avoided. In the same cells, the contraction which accompanies appropriate electrical activity can be monitored using optical methods. The purpose of this communication is to discuss the mechanisms of action of agents which exert an inotropic effect, paying particular attention to the analysis of electrical activity associated with contraction in individual cardiac myocytes. We have chosen to compare the actions of inotropic agents on myocytes from rats and guinea pigs since it appears that there are some differences in excitation-contraction coupling in these two species, and these differences may shed some additional light on inotropic mechanisms in ventricular muscle.


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  1. BLINKS, J.R., CAMILLE, B.O., JEWELL, B.R. & BRAVENY, P. (1972). Influence of caffeine and other methyl xanthines on mechanical properties of isolated mammalian heart muscle. Circ. Res., 30, 367–392.CrossRefGoogle Scholar
  2. BROWN, A.M., LEE, K.S. & POWELL, T. (1981). Sodium current in single rat heart muscle cells. J. Physiol., 318, 479–500.Google Scholar
  3. FABIATO, A. & FABIATO, F. (1979). Calcium and cardiac excitation-contraction coupling. A. Rev. Physiol., 41, 473–484.CrossRefGoogle Scholar
  4. HENDERSON, A., BRUTSAERT, D., FORMAN, R. & SONNENBLICK, E. (1974). Influence of caffeine on force-frequency relations in cat and in rat heart muscle. Cardiovasc. Res., 8, 162–172.CrossRefGoogle Scholar
  5. HESS, P. & WIER, W.G. (1984). Excitation-contraction coupling in cardiac purkinje fibers. Effects of caffeine on the intracellular [Ca2+] transient, membrane currents, and contraction. J. gen. Physiol., 83, 417–433.CrossRefGoogle Scholar
  6. HUME, J.R. & GILES, W. (1983). Ionic currents in single isolated bullfrog atrial cells. J. gen. Physiol., 81, 153–194.CrossRefGoogle Scholar
  7. ISENBERG, G. & KLOCKNER, U. (1982). Calcium currents of isolated bovine ventricular myocytes are fast and of large amplitude. Pflugers Arch., 395, 30–41.CrossRefGoogle Scholar
  8. JENDEN, DJ. & FAIRHURST, A.S. (1969). The pharmacology of ryanodine. Pharmac. Rev., 21, 1–25.Google Scholar
  9. JOSEPHSON, LR., SANCHEZ-CHAPULA, J. & BROWN, A.M. (1984). Early outward current in rat single ventricular cells. Circ. Res., 54, 157–162.CrossRefGoogle Scholar
  10. JOURDON, P., AUCLAIR, M.C. & LECHAT, P. (1982). Inotropic effects of caffeine in rat myocardium during the postnatal period. Dev. Pharmac. Ther., 4, suppl. 1, 173–181.Google Scholar
  11. KASS, R.S. (1981). An optical monitor of tension for small cardiac preparations. Biophys. J., 34, 165–170.CrossRefGoogle Scholar
  12. KASS, R.S. & WIEGERS, S.E. (1982). The ionic basis of concentration-related effects of noradrenaline on the action potential of calf cardiac purkinje fibres. J. Physiol, 322, 541–558.CrossRefGoogle Scholar
  13. LEE, K.S. & TSIEN, R.W. (1982). Reversal of current through calcium channels in dialysed single heart cells. Nature, 297, 498–501.CrossRefGoogle Scholar
  14. MARBAN, E. & TSIEN, R.W. (1982). Effects of nystatin-mediated intracellular ion substitution on membrane currents in calf purkinje fibres. J. Physiol., 329, 569–587.CrossRefGoogle Scholar
  15. 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. Circ. Res., 51, 142–151.CrossRefGoogle Scholar
  16. MITCHELL, M.R., POWELL, T., TERRAR, D.A. & TWIST, V.W. (1983). Characteristics of the second inward current in cells isolated from rat ventricular muscle. Proc. R. Soc. Lond. B., 219, 447–469.CrossRefGoogle Scholar
  17. MITCHELL, M.R., POWELL, T., TERRAR, D.A. & TWIST, V.W. (1984a). Strontium, nifedipine and 4-aminopyridine modify the time course of the action potential in cells from rat ventricular muscle. Br. J. Pharmac, 81, 551–556.CrossRefGoogle Scholar
  18. MITCHELL, M.R., POWELL, T., TERRAR, D.A. & TWIST, V.W. (1984b). The effects of ryanodine, EGTA and low-sodium on action potentials in rat and guinea-pig ventricular myocytes: evidence for two inward currents during the plateau. Br. J. Pharmac, 81, 543–550.CrossRefGoogle Scholar
  19. MITCHELL, M.R., POWELL, T., TERRAR, D.A. & TWIST, V.W. (1984c). Membrane potential and contraction in voltage-clamped cells from rat and guinea-pig ventricular muscle. J. Physiol., 346, 77P.Google Scholar
  20. MITCHELL, M.R., POWELL, T., TERRAR, D.A. & TWIST, V.W. (1984d). Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular cells. Br. J. Pharmac., 81, 13–15.CrossRefGoogle Scholar
  21. NOBLE, D. (1984). The surprising heart: A review of recent progress in cardiac electrophysiology. J. Physiol., 353, 1–50.CrossRefGoogle Scholar
  22. NOBLE, D. & TSIEN, R.W. (1969). Outward membrane currents activated in the plateau range of potentials in cardiac purkinje fibres. J. Physiol., 200, 205–231.CrossRefGoogle Scholar
  23. ORCHARD, C.H., EISNER, DA. & ALLEN, D.G. (1983). Oscillations of intracellular Ca in mammalian cardiac muscle. Nature, 304, 735–738.CrossRefGoogle Scholar
  24. POWELL, T., TERRAR, D.A. & TWIST, V.W. (1980). Electrical properties of individual cells isolated from adult rat ventricular myocardium. J. Physiol., 302, 131–153.Google Scholar
  25. POWELL, T., TERRAR, D.A. & TWIST, V.W. (1981). The effect of noradrenaline on slow inward current in rat ventricular myocytes. J. Physiol., 319, 82P.Google Scholar
  26. POWELL, T. & TWIST, V.W. (1976). A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium. Biochem. biophys. Res. Commun., 72, 327–333.CrossRefGoogle Scholar
  27. REUTER, H. (1973). Divalent cations as charge carriers in excitable membranes. Prog. Biophys. mol. Biol., 16, 1–43.CrossRefGoogle Scholar
  28. REUTER, H. (1979). Properties of two inward membrane currents in the heart. A. Rev. Physiol., 41, 413–424.CrossRefGoogle Scholar
  29. SUTKO, J.L., WILLERSON, J.T., TEMPLETON, C.H., JONES, L.R. & BESCH, H.R., Jr (1979). Ryanodine: its alterations of cat papillary muscle contractile state and responsiveness to inotropic interventions and a suggested mechanism of action. J. Pharmac. exp. Ther., 209, 37–47.Google Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • M. R. Mitchell
    • 1
  • T. Powell
    • 1
  • D. A. Terrar
    • 1
  • V. W. Twist
    • 1
  1. 1.Departments of Pharmacology and Therapeutics, and of Medical Physics and Institute of Nuclear MedicineMiddlesex Hospital Medical SchoolLondonUK

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