Frequency-Dependent Inhibition of the Intracellular Calcium Transients by Calmodulin Antagonists in the Aequorin-Injected Rabbit Papillary Muscle

  • Masao Endoh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 255)


Calmodulin, a ubiquitous functional protein in eukaryotic cells, has been found to play an essential role in regulation of enzymes and cellular processes in various tissues including smooth muscle cells (Cheung, 1980; Klee and Newton, 1985), Although it has been shown that calmodulin exists in myocardial cells and suggested that it may be involved in regulation of myocardial functions, based on the effects of calmodulin on enzyme activities and Ca2+uptake, its regulatory role in intact myocardium remains unclear. In order to get insight into the role of calmodulin in regulation of myocardial contractility, the effects of calmodulin antagonists, W-7 and trifluoperazine (TFP), on the intracellular calcium transients and isometric contractions were assessed simultaneously in the isolated rabbit papillary muscle, superficial cells of which had been microinjected with the Ca2+ sensitive bioluminescent protein aequorin.


Papillary Muscle Isometric Contraction Calcium Transient Stimulus Interval Myosin Light Chain Phosphorylation 
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  1. Aass, H., Skomedal, T., and Osnes, J.-B., 1983, Effects of trifluoperazine on ß-adrenergic responses of rat papillary muscle: related to calmodulin? Acta Pharmacol. et toxicol., 53:265.CrossRefGoogle Scholar
  2. Bayer, R., Hennekes, R., Kaufmann, R., and Mannhold, R., 1975, Inotropic and electrophysiological actions of verapamil and D600 in mammalian myocardium: I. Pattern of inotropic effects of the racemic compounds, Naunyn-Schmiedeberg’s Arch. Pharmacol., 290:49.CrossRefGoogle Scholar
  3. Bkaily, G., Sperelakis, N., Eldefrawi, M., 1984, Effects of the calmodulin inhibitor, trifluoperazine, on membrane potentials and slow action potentials of cultured heart cells, Eur. J. Pharmacol., 105:23.PubMedCrossRefGoogle Scholar
  4. Blinks, J. R., 1984, Methods for monitoring Ca++ concentrations with photoproteins in living cardiac cells, in: Methods in Studying Heart Membranes, vol. II, N. S. Dhalla, ed., Boca Raton, Fla., CRC Press, p. 237.Google Scholar
  5. Blinks, J. R., 1966, Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle, J. Pharmacol. Exp. Ther., 151:221.PubMedGoogle Scholar
  6. Blinks, J. R., Mattingly, P. H., Jewell, B. R., van Leeuwen, M., Harrer, G. C., and Allen, D. G., 1978, Practical aspects of the use of aequorin as a calcium indicator: assay, preparation microinjection, and interpretation of signals, Meth. Enzymol., 57:292.CrossRefGoogle Scholar
  7. Blinks, J. R., and Endoh, M., 1986, Modification of myofibrillar responsiveness to Ca++ as an inotropic mechanism, Circulation, 73(suppl. III):111–185.Google Scholar
  8. Bowditch, H. P., 1871, Uber die Eigentumlichkeiten der Reizbarkeit welche die Muskelfasern des Herzens zeigen, Ber. Sach. Wiss., 23:652.Google Scholar
  9. Brutsaert, D. L., and Claes, V. A., 1974, Onset of mechanical activation of mammalian heart muscle in calcium and strontium-containing solutions, Circ. Res., 35:345.PubMedGoogle Scholar
  10. Brutsaert, D. L., Be Clerck, N. M., Goethals, M. A., and Housmans, P. R., Relaxation of ventricular cardiac muscle, J. Physiol. (Lond.), 283:469.Google Scholar
  11. Caroni, P., and Carafoli, E., 1981, The Ca2+-pumping ATPase of heart sarcolemma: characterization, calmodulin dependence, and partial purification, J. Biol. Chem., 256:3263.PubMedGoogle Scholar
  12. Cheung, W. Y., 1980, Calmodulin plays a pivotal role in cellular regulation, Science, 207:19.PubMedCrossRefGoogle Scholar
  13. Fleckenstein, A., 1977, Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle, Ann. Rev. Pharmacol. Toxicol., 17:149.CrossRefGoogle Scholar
  14. Greenberg, D. A., Carpenter, C. L., and Messing, R. O., 1987, Interaction of calmodulin inhibitors and protein kinase C inhibitors with voltage-dependent calcium channels, Brain Res., 404:401.PubMedCrossRefGoogle Scholar
  15. Karaki, H., Murakami, K., Nakagawa, H., Ozaki, H., and Urakawa, N., 1982, Effects of calmodulin antagonists on tension and cellular calcium content in depolarized vascular and intestinal smooth muscles, Brit. J. Pharmacol., 77:661.Google Scholar
  16. Katz, S. and Remtulla, M. A., 1978, Phosphodiesterase protein activator stimulates calcium transport in cardiac microsomal preparations enriched in sarcoplasmic reticulum, Biochem. Biophys. Res. Commun., 83:1373.PubMedCrossRefGoogle Scholar
  17. Kenigsberg, R. L., Côté, A., Trifaró, J. M., 1982, Trifluoperazine, a calmodulin inhibitor, blocks secretion in cultured chromaffin cells at a step distal from calcium entry, Neuroscience, 7:2277.PubMedCrossRefGoogle Scholar
  18. Klee, C. B., and Newton, D. L., 1985, Calmodulin: an overview, in: Control and Manipulation of Calcium Movement, Parratt, J. R., Raven Press, New York, p. 131.Google Scholar
  19. Klein, I., 1983, Trifluoperazine inhibits the contraction of cultured rat cardiac cells and the phosphorylation of myosin light chain, J. Clin. Invest., 71:518.PubMedCrossRefGoogle Scholar
  20. Koch-Weser, J., and Blinks, J. R., 1963, The influence of the interval between beats on myocardial contractility, Pharmacol. Rev., 15:601.PubMedGoogle Scholar
  21. Le Peuch, C. J., Haiech, J., Démaille, J. G., 1979, Concerted regulation of cardiac sarcoplasmic reticulum calcium transport by cyclic adenosine monophosphate dependent and calcium-calmodulin-dependent phosphorylations, Biochemistry, 18:5150.PubMedCrossRefGoogle Scholar
  22. Luchowski, E. M., Yousif, F., Triggle, D. J., Maurer, S. C., Sarmiento, J. G., and Janis, R. A., 1984, Effects of metal cations and calmodulin antagonists on [3H] nitrendipine binding in smooth and cardiac muscle, J. Pharmacol. Exp. Ther., 230:607.PubMedGoogle Scholar
  23. Morgan, J. P., Wier, W. G., Hess, P., and Blinks, J. R., 1983, Influence of Ca++-channel blocking agents on calcium transients and tension development in isolated mammalian heart muscle, Circ. Res., 52(suppl. I):47.Google Scholar
  24. Sheu, S.-S., and Blaustein, M. P., 1986, Sodium/calcium exchange and regulation of cell calcium and contractility in cardiac muscle, with a note about vascular smooth muscle, in: The Heart and Cardiovascular System, Fozzard, H. A., Haber, E., Jennings, R. B., Katz, A. M., and Morgan, H. E., ed., Raven Press, New York, p. 509.Google Scholar
  25. Stoclet, J. C., Lugnier, C., Follenius, A., Scheftel, J. M., and Gerard, D., 1985, Calmodulin and calcium regulation: effect of antagonists, in: Calcium Entry Blockers and Tissue Protection, Godfraind, T., Vanhoutte, P. M., Govoni, S., and Paoletti, R., ed., Raven Press, New York, p. 31.Google Scholar
  26. Tada, M., Inui, M., Yamada, M., Kadoma, M., Kuzuya, T., Abe, H., and Kakiuchi, S., 1983, Effects of phospholamban phosphorylation catalyzed by adenosine 3′:5′-monophosphate-and calmodulin-dependent protein kinases on calcium transport ATPase of cardiac sarcoplasmic reticulum, J. Mol. Cell. Cardiol., 15:335.PubMedCrossRefGoogle Scholar
  27. Tkachuk, V. A., Baldenkov, G. N., Feoktistov, I. A., Men’shikov, M. Y., Quast, U., and Herzig, J. W., 1987, Metofenazate as a more selective calmodulin inhibitor than trifluoperazine, Arzneim.-Forsch/Drug Res., 37:1013.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Masao Endoh
    • 1
  1. 1.Department of PharmacologyYamagata University School of MedicineYamagataJapan

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