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Tension generation and relaxation in single myofibrils from human atrial and ventricular myocardium

  • Cardiovascular System
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Fast solution switching techniques in single myofibrils offer the opportunity to dissect and directly examine the sarcomeric mechanisms responsible for force generation and relaxation. The feasibility of this approach is tested here in human cardiac myofibrils isolated from small samples of atrial and ventricular tissue. At sarcomere lengths between 2.0 and 2.3 μm, resting tensions were significantly higher in ventricular than in atrial myofibrils. The rate constant of active tension generation after maximal Ca2+ activation (k ACT) was markedly faster in atrial than in ventricular myofibrils. In both myofibril types k ACT was the same as the rate of tension redevelopment after mechanical perturbations and decreased significantly by decreasing [Ca2+] in the activating solution. Upon sudden Ca2+ removal, active tension fully relaxed. Relaxation kinetics were (1) much faster in atrial than in ventricular myofibrils, (2) unaffected by bepridil, a drug that increases the affinity of troponin for Ca2+, and (3) strongly accelerated by small increases in inorganic phosphate concentration. The results indicate that myofibril tension activation and relaxation rates reflect apparent cross-bridge kinetics and their Ca2+ regulation rather than the rates at which thin filaments are switched on or off by Ca2+ binding or removal. Myofibrils from human hearts retain intact mechanisms for contraction regulation and tension generation and represent a viable experimental model to investigate function and dysfunction of human cardiac sarcomeres.

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References

  1. Hajjar RJ, Gwathmey JK, Briggs GM, Morgan JP (1988) Differential effect of DPI 201-106 on the sensitivity of the myofilaments to Ca2+ in intact and skinned trabeculae from control and myopathic human hearts. J Clin Invest 82:1578–1584

    PubMed  CAS  Google Scholar 

  2. Morano I, Bletz C, Wojciechowski R, Ruegg JC (1991) Modulation of crossbridge kinetics by myosin isoenzymes in skinned human heart fibers. Circ Res 68:614–618

    PubMed  CAS  Google Scholar 

  3. Zacharzowsky UB, Shah AM, Haase H, Morano I (1999) Inhibition of crossbridge function in the normal human heart by hypoxic endothelial superfusate. Biochem Biophys Res Commun 262:64–67

    Article  PubMed  CAS  Google Scholar 

  4. Mulieri LA, Barnes W, Leavitt BJ, Ittleman FP, LeWinter MM, Alpert NR et al (2002) Alterations of myocardial dynamic stiffness implicating abnormal crossbridge function in human mitral regurgitation heart failure. Circ Res 90:66–72

    Article  PubMed  CAS  Google Scholar 

  5. Narolska NA, van Loon RB, Boontje NM, Zaremba R, Penas SE, Russell J et al (2005) Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue. Cardiovasc Res 65:221–229

    Article  PubMed  CAS  Google Scholar 

  6. Wolff MR, Buck SH, Stoker SW, Greaser ML, Mentzer RM (1996) Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: role of altered beta-adrenergically mediated protein phosphorylation. J Clin Invest 98:167–176

    PubMed  CAS  Google Scholar 

  7. van Der Velden J, Klein LJ, Zaremba R, Boontje NM, Huybregts MA, Stooker W et al (2001) Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts. Circulation 104:1140–1146

    Google Scholar 

  8. Borbely A, van der Velden J, Papp Z, Bronzwaer JGF, Edes I, Stienen GJM et al (2005) Cardiomyocyte stiffness in diastolic heart failure. Circulation 111:774–781

    Article  PubMed  Google Scholar 

  9. Poggesi C, Tesi C, Stehle R (2005) Sarcomeric determinants of striated muscle relaxation kinetics. Invited Review. Pflügers Arch 449:505–517

    Article  PubMed  CAS  Google Scholar 

  10. Linke WA, Popov VI, Pollack GH (1994) Passive and active tension in single cardiac myofibrils. Biophys J 67:782–792

    PubMed  CAS  Google Scholar 

  11. Colomo F, Piroddi N, Poggesi, C, te Kronnie KG, Tesi C (1997) Active and passive forces of isolated myofibrils from cardiac and fast skeletal muscle of the frog. J Physiol 500:535–548

    PubMed  CAS  Google Scholar 

  12. Stehle R, Krueger M, Pfitzer G (2002) Force kinetics and individual sarcomere dynamics in cardiac myofibrils following rapid Ca2+ changes. Biophys J 83:2152–2161

    PubMed  CAS  Google Scholar 

  13. Sachs F (1999) Practical limits on the maximal speed of solution exchange for patch clamp experiments. Biophys J 77:682–690

    PubMed  CAS  Google Scholar 

  14. Tesi C, Colomo F, Nencini S, Piroddi N, Poggesi, C (2000) The effect of inorganic phosphate on force generation in single myofibrils from rabbit skeletal muscle. Biophys J 78:3081–3092

    PubMed  CAS  Google Scholar 

  15. Tesi C, Piroddi N, Colomo F, Poggesi C (2002) Relaxation kinetics following sudden Ca2+ reduction in single myofibrils from skeletal muscle. Biophys J 83:2142–2151

    PubMed  CAS  Google Scholar 

  16. Cazorla O, Freiburg A, Helmes M, Centner T, McNabb M, Wu Y et al (2000) Differential expression of cardiac titin isoforms and modulation of cellular stiffness. Circ Res 86:59–67

    PubMed  CAS  Google Scholar 

  17. Reiser PJ, Portman MA, Ning XH, Schomisch Moravec C (2001) Human cardiac myosin heavy chain isoforms in fetal and failing adult atria and ventricles. Am J Physiol 280:H1814–H1820

    CAS  Google Scholar 

  18. Gordon AM, Homsher E, Regnier M (2000) Regulation of contraction in striated muscle. Physiol Rev 80:853–924

    PubMed  CAS  Google Scholar 

  19. Solaro RJ, Bousquet P, Johnson JD (1986) Stimulation of cardiac myofilament force, ATPase activity and troponin C Ca++ binding by bepridil. J Pharmacol Exp Ther 238:502–507

    PubMed  CAS  Google Scholar 

  20. MacLachlan LK, Reid DG, Mitchell RC, Salter CJ, Smith SJ (1990) Binding of a calcium sensitizer, bepridil, to cardiac troponin C. A fluorescence stopped-flow kinetic, circular dichroism, and proton nuclear magnetic resonance study. J Biol Chem 265:9764–9770

    PubMed  CAS  Google Scholar 

  21. Neagoe C, Kulke M, del Monte F, Gwathmey JK, de Tombe PP, Hajjar RJ et al (2002) Titin isoform switch in ischemic human heart disease. Circulation 106:1333–1341

    Article  PubMed  Google Scholar 

  22. Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S et al (2004) Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation 110:155–162

    Article  PubMed  CAS  Google Scholar 

  23. Backx PH, Gao WD, Azan-Backx MD, Marban E (1995) The relationship between contractile force and intracellular [Ca2+] in intact rat cardiac trabeculae. J Gen Physiol 105:1–19

    Article  PubMed  CAS  Google Scholar 

  24. Stehle R, Kruger M, Scherer P, Brixius K, Schwinger RH, Pfitzer G (2002) Isometric force kinetics upon rapid activation and relaxation of mouse, guinea-pig and human heart muscle studied on the subcellular myofibrillar level. Basic Res Cardiol 97(Suppl 1):I127–I135

    PubMed  Google Scholar 

  25. van der Velden J, Klein LJ, van der Bijl M, Huybregts MAJM, Stooker W, Witkop J et al (1999) Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart. Cardiovasc Res 42:706–719

    Article  PubMed  Google Scholar 

  26. Moss RL, Razumova M, Fitzsimmons DP (2004) Myosin cross bridge activation of cardiac thin filaments: implications for myocardial function in health and disease. Circ Res 94:1290–1300

    Article  PubMed  CAS  Google Scholar 

  27. van der Velden J, Papp Z, Boontje NM, de Jong JW, Janssen PML, Hasenfuss G et al (2003) The effect of myosin light chain 2 dephosphorylation on Ca2+-sensitivity of force is enhanced in failing human hearts. Cardiovasc Res 57:505–514

    Article  PubMed  Google Scholar 

  28. Morano M, Zacharzowski U, Maier M, Lange PE, Alexi-Meskishvili V, Haase H et al (1996) Regulation of human heart contractility by essential myosin light chain isoforms. J Clin Invest 98:467–473

    Article  PubMed  CAS  Google Scholar 

  29. Bottinelli R, Canepari M, Cappelli V, Reggiani C (1995) Maximum speed of shortening and ATPase activity in atrial and ventricular myocardia of hyperthyroid rats. Am J Physiol 269:C785–C790

    PubMed  CAS  Google Scholar 

  30. Buck SH, Konyn PJ, Palermo J, Robbins J, Moss RL (1999) Altered kinetics of contraction of mouse atrial myocytes expressing ventricular myosin regulatory chain. Am J Physiol 276:H1167–H1171

    PubMed  CAS  Google Scholar 

  31. Li Y, Love ML, Putkey JA, Cohen C (2000) Bepridil opens the regulatory N-terminal lobe of cardiac troponin C. Proc Natl Acad Sci USA 97:5140–5145

    Article  PubMed  CAS  Google Scholar 

  32. Brenner B (1988) Effect of Ca2+ on cross bridge turnover kinetics in skinned single rabbit psoas fibers: implication for regulation of muscle contraction. Proc Natl Acad Sci USA 83:3265–3269

    Article  Google Scholar 

  33. Brenner B, Chalovich JM (1999) Kinetics of thin filament activation probed by fluorescence of N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1, 3-diazole-labeled troponin I incorporated into skinned fibers of rabbit psoas muscle: implications for regulation of muscle contraction. Biophys J 77:2692–2708

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by Telethon–Italy (grant # GGP02428), Ministero Istruzione Università e Ricerca (PRIN2004), and European Union (STREP Project “NORMACOR,” 6th European Framework Program, contract LSH M/CT/2006/018676). The contents of this work are solely the responsibility of the authors and do not necessarily represent an official view of awarding organizations.

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Authors and Affiliations

  1. Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (CIMMBA), Firenze, Italy

    Nicoletta Piroddi, Alexandra Belus, Beatrice Scellini, Chiara Tesi, Gabriele Giunti, Elisabetta Cerbai, Alessandro Mugelli & Corrado Poggesi

  2. Dipartimento di Scienze Fisiologiche, Università di Firenze, Viale Morgagni 63, 50134, Firenze, Italy

    Nicoletta Piroddi, Alexandra Belus, Beatrice Scellini, Chiara Tesi & Corrado Poggesi

  3. Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Firenze, Italy

    Elisabetta Cerbai & Alessandro Mugelli

  4. Divisione di CardioChirurgia, Ospedale Careggi, Firenze, Italy

    Gabriele Giunti

Authors
  1. Nicoletta Piroddi
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  2. Alexandra Belus
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  3. Beatrice Scellini
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  4. Chiara Tesi
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  8. Corrado Poggesi
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Correspondence to Corrado Poggesi.

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Piroddi, N., Belus, A., Scellini, B. et al. Tension generation and relaxation in single myofibrils from human atrial and ventricular myocardium. Pflugers Arch - Eur J Physiol 454, 63–73 (2007). https://doi.org/10.1007/s00424-006-0181-3

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  • DOI: https://doi.org/10.1007/s00424-006-0181-3

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