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Is Titin the Length Sensor in Cardiac Muscle? Physiological and Physiopathological Perspectives

  • Jean-Yves Le Guennec
  • Olivier Cazorla
  • Alain Lacampagne
  • Guy Vassort
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 481)

Abstract

One of the most salient physiological characteristics of cardiac muscle is that a dilated heart pumps more vigorously, a phenomenon known as the Frank-Starling relationship (see Allen and Kentish, 1985). At least two cellular mechanisms participate in this phenomenon: the reduction of the interfilament lattice spacing which favors the formation of cross-bridges (Wang and Fuchs, 1995) and the increased affinity of troponin C (TnC) for calcium (Ca2+) (Babu et al., 1988). In the latter case, it has been established that TnC itself is not the length sensor (Moss et al., 1991). The intracellular structure(s) able to sense changes in cell length has always been challenged and is still not known. We previously observed on intact isolated cardiac cells that active tension is more closely related to passive tension than to sarcomere length per se (Cazorla et al., 1997). This might have some physiological implications in the working heart since we found that sub-epicardial cells are more supple than sub-endocardial cells. In the present work on skinned cells, we studied the relationship between different levels of passive tension (modulated by a mild trypsin digestion) and the shift in pCa50 of tension-pCa relations induced by a stretch of cells from 1.9 to 2.3 μm sarcomere length. A significant correlation was obtained between passive tension and the stretch-induced shift in pCa50, or stretch-sensitivity of the active force. These observations led us to assume that titin might play a role in sensing cell length to modulate the contractile activity. Besides, it is known that myocardial infarcted cells are less sensitive to stretch. We propose that, in such a rat model, alterations of titin might participate in heart failure.

Keywords

Active Force Cardiac Cell Sarcomere Length Active Tension Passive Tension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allen D, Kentish J. The cellular basis of the length-tension relation in cardiac muscle. J Mol Cell Cardiol 1985;17:821–840.PubMedCrossRefGoogle Scholar
  2. Astier C, Raynaud F, Lebart M-C, Roustan C, Benyamin, Y. Binding of a native titin fragment to actin is regulated by PIP2. FEBS Letters 1998;429:95–98.PubMedCrossRefGoogle Scholar
  3. Babu A, Sonnenblick E, Gulati J. Molecular basis of the influence of muscle length on myocardial performance. Science 1988;240:74–76.PubMedCrossRefGoogle Scholar
  4. Cazorla O, Pascarel C, Gamier D, Le Guennec J-Y Resting tension participates in the modulation of active tension in isolated guinea pig ventricular myocytes. J Mol Cell Cardiol 1997;29:1629–1637.PubMedCrossRefGoogle Scholar
  5. Cazorla O, White E, Le Guennec J-Y Regional differences in the passive properties in single rat and ferret ventricular myocytes. Biophys J, 1998;74: A155.Google Scholar
  6. Cazorla O, Vassort G, Gamier D, Le Guennec J-Y Length modulation of active force in rat cardiac myocytes: Is titin the sensor? J Mol Cell Cardiol, 1999;31:1215–1227.PubMedCrossRefGoogle Scholar
  7. Freiburg A, Gautel M. A molecular map of the interactions between titin and myosin-binding protein C. Eur J Biochem 1996;235:317–323.PubMedCrossRefGoogle Scholar
  8. Gannier F, White E, Lacampagne A, Gamier D, Le Guennec J-Y. Streptomycin reverses a large stretch-induced increase in [Ca2+]. in isolated guinea-pig ventricular myocytes. Cardiovasc Res 1994;28:1193–1198.PubMedCrossRefGoogle Scholar
  9. Gannier F, White E, Gamier D, Le Guennec J-Y. A possible mechanism for large stretch-induced increases in [Ca2+]. in isolated guinea-pig ventricular myocytes. Cardiovasc Res 1996;32:158–167.PubMedGoogle Scholar
  10. Granzier H, Irving T. Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments. Biophys J 1995;68:1027–1044.PubMedCrossRefGoogle Scholar
  11. Helmes M, Trombitás K, Granzier H. Titin develops restoring force in rat cardiac myocytes. Circ Res 1996;79:619–626.PubMedCrossRefGoogle Scholar
  12. Horowits R, Kempner E, Bisher M, Podolsky R. A physiological role for titin and nebulin in skeletal muscle. Nature 1986;626:160–164.CrossRefGoogle Scholar
  13. Houmeida A, Tskhovrebova L, Trinick J. Studies of the interaction between titin and myosin. J Cell Biol 1995;131:1471–1481.PubMedCrossRefGoogle Scholar
  14. Kellermayer M, Granzier H. Calcium-dependent inhibition of in vitro thin-filament motility by native titin. FEBS Letters 1996;380:281–286.PubMedCrossRefGoogle Scholar
  15. Labeit S, Kolmerer B. Titins, giant proteins in charge of muscle ultrastructure and elasticity. Science 1995;270:293–296.PubMedCrossRefGoogle Scholar
  16. Labeit S, Kolmerer B, Linke W. The giant protein titin. Emerging roles in physiology and pathophysiology. Circ Res 1997;80:290–294.PubMedCrossRefGoogle Scholar
  17. Le Guennec J-Y, Peineau N, Argibay J, Mongo K, Gamier D. A new method of attachment of isolated mammalian ventricular myocytes for tension recording: length dependence of passive and active tension. J Mol Cell Cardiol 1990;22:1083–1093.PubMedCrossRefGoogle Scholar
  18. Linke W, Ivemeyer M, Olivieri N, Kolmerer B, Rüegg J, Labeit S. Towards a molecular understanding of the elasticity of titin. J Mol Biol 1996;261:62–71.PubMedCrossRefGoogle Scholar
  19. Linke W, Ivemeyer M, Labeit S, Hinssen H, Rüegg J, Gautel M. Actin-titin interaction in cardiac myofibrils: probing a physiological role. Biophys J 1997;73:905–919.PubMedCrossRefGoogle Scholar
  20. Linke W, Ivemeyer M, Mündel P, Stockmeier M, Kolmerer B. Nature of PEVK-titin elasticity in skeletal muscle. PNAS USA 1998;95:8052–8057.PubMedCrossRefGoogle Scholar
  21. Maruyama K, Natori R, Nonomura Y. New elastic protein from muscle. Nature 1976;262:58–60PubMedCrossRefGoogle Scholar
  22. Mayans O, Van Der Ven P, Wilm M, Mues A, Young P, Fürst D, Wilmanns M, Gautel M. Structural basis for activation of the titin kinase domain during myofibrillogenesis. Nature 1998;395:863–869.PubMedCrossRefGoogle Scholar
  23. Morano I, Hädicke K, Grom S, Koch A, Schwinger R, Böhm M, Bartel S, Erdmann E, Krause E. Titin, myosin light chains and C-protein in the developing and failing human heart. J Mol Cell Cardiol 1994;26:361–368.PubMedCrossRefGoogle Scholar
  24. Moss R, Nwoye L, Greaser M. Substitution of cardiac troponin C into rabbit muscle does not alter the length dependence of Ca2+ sensitivity of tension. J Physiol (Lond) 1991;440:273–289.Google Scholar
  25. Obermann W, Gautel M, Weber K, Fürst D. Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin. EMBO J 1997;16:211–220.PubMedCrossRefGoogle Scholar
  26. Pucéat M, Clément O, Lechêne P, Pelosin J, Ventura-Clapier R, Vassort G. Neurohormonal control of calcium sensitivity of myofilaments in rat skinned heart cells. Circ Res 1990;67:517–524.PubMedCrossRefGoogle Scholar
  27. Schwinger R, Böhm M, Koch A, Schmidt U, Morano I, Eissner H, Überfuhr P, Reichart B, Erdmann E. The failing human heart is unable to use the Frank-Starling mechanism. Circ Res 1994;74:959–969.PubMedCrossRefGoogle Scholar
  28. Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Marayama K, Susuki K. Muscle-specific calpain, p94, responsible for limb girdlemuscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J Biol Chem 1995;270:31158–31162.PubMedCrossRefGoogle Scholar
  29. Sorimachi H, Freiburg A, Kolmerer B, Ishiura S, Stier G, Gregoro C, Labeit D, Linke W, Susuki K, Labeit S. Tissue-specific expression and ±-actinin binding properties of the Z-disc titin: implications for the nature of vertebrate Z-disks. J Mol Biol 1997;270:688–695.PubMedCrossRefGoogle Scholar
  30. Soteriou A, Gamage M, Trinick J. A survey of the interactions made by titin. J Cell Science 1993;14:119–123.Google Scholar
  31. Stuyvers B, Miura M, Jin J-P, Ter Keurs H. Ca2+-dependence of diastolic properties of cardiac sarcomeres: involvement of titin. Progress Biophys Mol Biol 1998;69:425–443.CrossRefGoogle Scholar
  32. Trombitás K, Granzier H. Actin removal from cardiac myocytes shows that near Z line titin attaches to actin while under tension. Am J Physiol 1997;273:C662–C670.PubMedGoogle Scholar
  33. Trombitas K, Greaser M, Pollack G. Interaction between titin and thin filaments in intact cardiac muscle. J Muscle Res Cell Motil 1997;18:345–351.PubMedCrossRefGoogle Scholar
  34. Wang Y-P, Fuchs F. Osmotic compression of skinned cardiac and skeletal muscle bundles: Effects on force generation, Ca2+ sensitivity and Ca2+ binding. J Mol Cell Cardiol 1995;27:1235–1244.PubMedCrossRefGoogle Scholar
  35. Yoshioka T, Higuchi H, Kimura S, Ohashi K, Umazume Y, Maruyama K. Effects of mild trypsin treatment on the passive tension generation and connectin splitting in stretched skinned fibers from frog skeletal muscle. Biomed Res 1986;7:181–186.Google Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Jean-Yves Le Guennec
    • 1
  • Olivier Cazorla
    • 1
  • Alain Lacampagne
    • 2
  • Guy Vassort
    • 2
  1. 1.Laboratoire de Physiopathologie CardiovasculaireMontpellierFrance
  2. 2.Laboratoire de Physiologie des Cellules Cardiaques et VasculairesToursFrance

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