Advertisement

Basic Research in Cardiology

, Volume 83, Issue 4, pp 343–349 | Cite as

Are isolated cardiomyocytes a suitable experimental model in all lines of investigation in basic cardiology?

  • H. Kammermeier
  • H. Rose
Editorial

Summary

Isolated cardiac myocytes of adult rats resemble the intact myocardium in many respects. Thus, use of isolated cells has been established in many lines of basic cardiological research. In electrophysiology, ionic channels can apparently be characterized more accurately than in intact tissue. The transport of metabolites across the sarcolemma can be studied independently of the influence of other types of cells and transport barriers. However, most reports about metabolism deal with quiescent cells, which obviously have a very low metabolic rate, provided they are intact, and their oxidative phosphorylation is not uncoupled. Thus, their application as a model of a working heart appears to be restricted. But using electrical stimulation, the metabolic activity of the cells can be gradually enhanced up to those values observed in beating hearts. In this case, the measurement of mechanical parameters as the myocytes respond to the electrical stimulation is of interest. The combination of the measurements of both metabolic and mechanical parameters in a physical model, led us to investigate the possibility of measuring inotropic effects as well as the relationship between mechanical changes and changes in oxygen consumption, e.g. as a result of the utilization of different substrates. This expands the application of the model to pharmacology, in which the influence of the mechanical action of the heart and its oxygen consumption is of major interest. If the model of isolated cardiomyocytes is employed in screening studies, a reduction in the number of experimental animals required for this line of rescarch will inevitably result.

Key words

cardiomyocytes inotropie effects cardiacmetabolism regulation electrical stimulation ofcardiomyocytes 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bailey IA, von Tscharner V, Harris DR (1985) Non-invasive measurement of cell surface receptors. Basic Res Cardiol 80, S1:43–46PubMedGoogle Scholar
  2. 2.
    Bihler I, McNevin SR, Sawh PC (1985) Regulation of glucose transport in Ca++-tolerant myocytes from adult rat heart. Biochim Biophys Acta 846:208–215CrossRefPubMedGoogle Scholar
  3. 3.
    Brady AJ, Tan ST, Ricchinti NV (1979) Contractile force measured in unskinned adult rat heart fibres. Nature 282:728–729CrossRefPubMedGoogle Scholar
  4. 4.
    Bretschneider HJ, Hellige G (1976) Ventrikelkontraktion — Kontraktilität, Inotropie, Suffizienzgrad und Arbeitsökonomie des Herzens. Verh dtsch Ges Kreisl Forsch 42:14–30Google Scholar
  5. 5.
    Brown AM, Lee KS, Powell T (1980) Reactivation of sodium conductance in single heart muscle cells. J Physiol 301:78–79Google Scholar
  6. 6.
    Bustamente JO, Watanabe T, McDonald TF (1981) Single cells from adult mammalian heart: isolation procedure and preliminary electrophysiological studies. Can J Physiol Pharmacol 59:907–910PubMedGoogle Scholar
  7. 7.
    DeGrella RF, Light RJ (1985) Uptake of fatty acids by isolated heart myocytes. Basic Res Cardiol 80, S2:107–110CrossRefGoogle Scholar
  8. 8.
    Dow JW, Harding NGL, Powell T (1981) Isolated cardiac myocytes: II. Functional aspects of mature cells. Cardiovasc Res 15:549–579PubMedGoogle Scholar
  9. 9.
    Eckel J, Reinauer H (1980) Characteristics of insulin receptors in the heart muscle binding of insulin to isolated muscle cells from adult rat heart. Biochem Biophys Acta 629:510–521PubMedGoogle Scholar
  10. 10.
    Eckel J, Pandalis G, Reinauer H (1983) Insulin action on glucose transport system in isolated cardiocytes from adult rat. Biochem J 212:385–392PubMedGoogle Scholar
  11. 11.
    Eckel J, Reinauer H (1985) The insulin receptor of adult heart muscle cells. Basic Res Cardiol 80, S1:61–64Google Scholar
  12. 12.
    Eckel J, Reinauer H (1985) Glucose uptake in isolated heart cells: studies on the role of insulin. Basic Res Cardiol 80, S2:103–106PubMedGoogle Scholar
  13. 13.
    Fabiato A, Fabiato F (1972) Excitation-contraction coupling of isolated cardiac fibres with disrupted or closed sarcolcmmas. Cire Res 31, 3:293–307Google Scholar
  14. 14.
    Gerards P, Graf W, Kammermeier H (1982) Glucose transfer studies in isolated cardiocytes of adult rats. J Mol Cell Cardiol 14:141–149CrossRefPubMedGoogle Scholar
  15. 15.
    Haworth RA, Hunter DR, Berkoff HA, Moss RL (1983) Metabolic cost of stimulated beating of isolated adult rat heart cells in suspension. Circ Res 52:342–351PubMedGoogle Scholar
  16. 16.
    Haworth RA, Hunter DR, Berkoff H (1985) Modulation of uncoupler-induced sugar uptake in isolated adult heart cells by isoproterenol. Arch Biochem Biophys 239, 1:191–199CrossRefPubMedGoogle Scholar
  17. 17.
    Haworth RA, Berkoff HA (1986) The control of sugar uptake by metabolic demand in isolated adult rat heart cells. Circ Res 58:157–165PubMedGoogle Scholar
  18. 18.
    Hütter JF, Piper HM, Spiekermann PG (1983) A new method for continuous measuring of respiratory quotient in a computer-assisted working heart preparation. Basic Res Cardiol 78:1–7CrossRefPubMedGoogle Scholar
  19. 19.
    Hütter JF, Schweickhardt C, Piper HM, Spickermann PG (1984) Inhibition of fatty acid oxidation and decrease of oxygen consumption of working rat heart by 4-bromocrotonic acid. J Mol Cell Cardiol 16:105–108PubMedGoogle Scholar
  20. 20.
    Hütter JF, Piper HM, Spickermann PG (1984) Myocardial fatty acid oxydation: evidence for an albumin-receptor-mediated membrane transfer of fatty acids. Basic Res Cardiol 79:274–282CrossRefPubMedGoogle Scholar
  21. 21.
    Isenberg G, Klöckner U (1980) Glycocalix is not required for slow inward calcium current in isolated rat heart myocytes. Nature 284:358–360CrossRefPubMedGoogle Scholar
  22. 22.
    Isenberg G, Klöckner U (1985) The electrophysiological properties of the isolated adult heart cell: an overview. Basic Res Cardiol 80, S2:51–54PubMedGoogle Scholar
  23. 23.
    Jacobson SL, Piper HM (1986) Cell cultures of adult cardiomyocytes as models of the myocardium. J Mol Cell Cardiol 18:661–678PubMedGoogle Scholar
  24. 24.
    Kammermeier H, Wein B, Graf W (1985) Characteristics of lactate transfer in isolated cardiac myocytes. Basic Res Cardiol 80, S1:57–60PubMedGoogle Scholar
  25. 25.
    Kammermeier H, Wein B, Gerards P, Lang U, Wendtland B, Schmitz D, Rose H (1985) Barriers in cardiac substrate supply. Basic Res Cardiol 80, S2:89–92PubMedGoogle Scholar
  26. 26.
    Kerebey AL, Vary TC, Randle PJ (1985) Molecular mechanisms regulating myocardial glucose oxydation. Basic Res Cardiol 80, S2:93–96Google Scholar
  27. 27.
    Korb H, Hoeft A, Hunneman DH, Schraeder R, Wolper W, Hellige G (1984) Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(s)-4-hydroxyphenylglycine]. Naunyn-Schmiedeberg's Arch Pharmacol 327:70–74CrossRefGoogle Scholar
  28. 28.
    Lau YH, Robinson RB, Rosen MR, Bilenzitian JP (1980) Subclassification of β-adrenergic receptors in cultured rat cardiac myoblasts and fibroblasts. Circ Res 47:41–48PubMedGoogle Scholar
  29. 29.
    Lee KS, Weeks TA, Kao RL, Aaike N, Brown AM (1979) Sodium current in single heart muscle cells. Nature 278:269–271CrossRefPubMedGoogle Scholar
  30. 30.
    Morgan HE, Randle PJ, Regen DM (1959) Regulation of glucose uptake by muscle. Biochem J 73:573–579PubMedGoogle Scholar
  31. 31.
    Morgan HE, Regen DM, Park CR (1964) Identification of a carrier-mediated sugar transport system in muscle. J Biol Chem 239:369–373PubMedGoogle Scholar
  32. 32.
    Moustafa E, Giachetti A, Downey HF, Bashour FA (1978) Binding of (3H) Dihydroalprenolol to β-adrenoreceptors of cells isolated from adult rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303:107–109CrossRefGoogle Scholar
  33. 33.
    Oronato JJ, Rudolph SA (1981) Regulation of protein phosphorylation by inotropic agents in isolated rat myocardial cells. J Biol Chem 256:10697–10703PubMedGoogle Scholar
  34. 34.
    Pearce FJ, Forster J, DeLecuw G, Williamson JR, Tutwiler GF (1979) Inhibition of fatty acid oxydation in normal and hypoxic perfused rat hearts by 2-tetradecylglycidic acid. J Mol Cell Cardiol 11:893–915CrossRefPubMedGoogle Scholar
  35. 35.
    Pelzer D, Cavalié A, Trautwein W (1985) Cardiac Ca++ channel currents at the level of single cells and single channels. Basic Res Cardiol 80, S2:65–70Google Scholar
  36. 36.
    Powell T, Terrar DA, Twist VW (1980) Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol 302:131–153PubMedGoogle Scholar
  37. 37.
    Rieser G, Sabbadini R, Paolini P, Fry M, Inesi G (1979) Sarcomere motion in isolated cardiac cells. Am J Physiol 236:C70–77PubMedGoogle Scholar
  38. 38.
    Rose H, Kammermeier H (1985) Electrically stimulated adult rat cardiac myocytes: substrate metabolism, oxygen consumption and contractile behavior. Pflügers Arch 405, S2:R17 abstrCrossRefGoogle Scholar
  39. 39.
    Rose H, Kammermeier H (1986) Contraction and metabolic activity of electrically stimulated cardiac myocytes from adult rats. Pflügers Arch 407:116–118CrossRefGoogle Scholar
  40. 40.
    Spiekermann PG, Piper HM (1985) Oxygen demand of calcium-tolerant adult cardiac myocytes. Basis Res Cardiol 80, S2:71–74Google Scholar
  41. 41.
    Wilson DL, Lacerda AE, Kunze DL, Brown AM (1985) Single channel and whole cell sodium currents in heart cells. Basic Res Cardiol 80, S2:61–64CrossRefGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag 1988

Authors and Affiliations

  • H. Kammermeier
    • 1
  • H. Rose
    • 1
  1. 1.Abteilung PhysiologieMedizinische Fakultät der RWTH AachenAachenF.R.G.

Personalised recommendations