Ca2+ -currents and intracellular [Ca2+]i-transients in single ventricular myocytes isolated from terminally failing human myocardium

  • Dirk J. Beuckelmann
  • E. Erdmann


The purpose of the present study was to test the hypothesis that steps between the excitation of the cell membrane and contraction are altered in cardiac failure. Ca2+-currents and [Ca2+]-transients were measured in single ventricular myocytes isolated from explanted hearts of patients with terminal heart failure undergoing transplantation, or from donors whose organs could not be used for technical reasons.

Peak Ca2+-current densities were unchanged, as was the current-voltage relation. However, in myocytes isolated from severely failing hearts resting [Ca2+]i-levels were elevated, peak [Ca2+]i-transients were significantly smaller, and the diastolic decline of [Ca2+]i was markedly slowed.

As the trigger for the release of Ca2+ from the sarcoplasmic reticulum is unchanged and the systolic [Ca2+]i-transient is reduced, severe heart failure can be described as partial electromechanical uncoupling.

Key words

Human ventricular myocyte heart failure [Ca2+]i –handling Ca2+ -current fura-2 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beuckelmann DJ, Näbauer M, Erdmann E (1991) Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol 23: 929–937PubMedCrossRefGoogle Scholar
  2. 2.
    Beuckelmann DJ, Wier WG (1988) Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Phys (Lond) 405: 233–255Google Scholar
  3. 3.
    Böhm M, Beuckelmann D, Brown L, Feiler G, Lorenz B, Näbauer M, Kemkes B and Erdmann E. (1988) Reduction of beta-adrenoceptor density and evaluation of positive inotropic responses in isolated, diseased human myocardium. Eur Heart J 9: 844–852PubMedGoogle Scholar
  4. 4.
    Böhm M, Gieschik P, Jakobs KH, Pieske B, Schnabel P, Ungerer M and Erdmann E. (1990) Increase of Gia in human hearts with dilated but not ischemic cardiomyopathy. Circulation 82: 1249–1265PubMedCrossRefGoogle Scholar
  5. 5.
    Fabiato A (1985) Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J Gen Physiol 85: 291–320PubMedCrossRefGoogle Scholar
  6. 6.
    Feldman AM, Cates AE, Bristow MR and Van Dop C (1989) Altered expression of α-subunits of G proteins in failing human hearts. J Mol Cell Cardiol 21: 359–365PubMedCrossRefGoogle Scholar
  7. 7.
    Feldman MD, Copelas L, Gwathmey JK, Phillips P, Warren SE, Schoen FJ, Grossman W and Morgan JP (1987) Deficient production of cyclic AM Pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 75 (2): 331–339PubMedCrossRefGoogle Scholar
  8. 8.
    Gwathmey JK, Copelas L, Mackinnon R, Schoen FJ, Feldman MD, Grossman W and Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61: 70–76PubMedGoogle Scholar
  9. 9.
    Hamill OP, Marty A, Neher E, Sakmann B and Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391: 85–100PubMedCrossRefGoogle Scholar
  10. 10.
    Holmberg SRM and Williams A J (1989) Single channels recordings from human cardiac sarcoplasmic reticulum. Circ Res 65: 1445–1449PubMedGoogle Scholar
  11. 11.
    Limas CJ, Olivari M-T, Goldenberg IF, Levine TB, Benditt DG and Simon A (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardio vase Res 21: 601–605CrossRefGoogle Scholar
  12. 12.
    Movsesian MA, Bristow MR and Krall J (1989) Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy. Circ Res 65: 1141–1144PubMedGoogle Scholar
  13. 13.
    Näbauer M, Böhm M, Brown L, Diet F, Eichhorn M, Kemkes B, Pieske B and Erdmann E (1988) Positive inotropic effects in isolated ventricular myocardium from non-failing and terminally failing hearts. Eur J Clin Invest 18: 600–606PubMedCrossRefGoogle Scholar
  14. 14.
    Rasmussen PR, Minobe W and Bristow MR (1990) Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium. Biochem Pharmacol 39: 691–696PubMedCrossRefGoogle Scholar
  15. 15.
    Wankerl M, Böhm M, Morano I, Rüegg JC, Eichhorn M and Erdmann E (1990) Calcium sensitivity and myosin light chain pattern of atrial and ventricular skinned cardiac fibers from patients with various kinds of cardiac disease. J Mol Cell Cardiol 22: 1425–1438PubMedCrossRefGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co.KG, Darmstadt 1992

Authors and Affiliations

  • Dirk J. Beuckelmann
    • 1
    • 2
  • E. Erdmann
    • 1
  1. 1.Department of Medicine IUniversity of MunichGermany
  2. 2.Medizinische Klinik IUniversität München Klinikum GroßhadernMünchen 70Germany

Personalised recommendations