Skip to main content
SpringerLink
Log in

The interdependence of Ca2+ activation, sarcomere length, and power output in the heart

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Myocardium generates power to perform external work on the circulation; yet, many questions regarding intermolecular mechanisms regulating power output remain unresolved. Power output equals force × shortening velocity, and some interesting new observations regarding control of these two factors have arisen. While it is well established that sarcomere length tightly controls myocyte force, sarcomere length–tension relationships also appear to be markedly modulated by PKA-mediated phosphorylation of myofibrillar proteins. Concerning loaded shortening, historical models predict independent cross-bridge mechanics; however, it seems that the mechanical state of one population of cross-bridges affects the activity of other cross-bridges by, for example, recruitment of cross-bridges from the non-cycling pool to the cycling force-generating pool during submaximal Ca2+ activation. This is supported by the findings that Ca2+ activation levels, myofilament phosphorylation, and sarcomere length are all modulators of loaded shortening and power output independent of their effects on force. This fine tuning of power output probably helps optimize myocardial energetics and to match ventricular supply with peripheral demand; yet, the discernment of the chemo-mechanical signals that modulate loaded shortening needs further clarification since power output may be a key convergent point and feedback regulator of cytoskeleton and cellular signals that control myocyte growth and survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ait Mou Y, le Guennac J-Y, Mosca E, de Tombe PP, Cazorla O (2008) Differential contribution of cardiac sarcomeric proteins in the myofibrillar force response to stretch. Pflugers Arch 457:25–36

    Article  PubMed  CAS  Google Scholar 

  2. Cazorla O, Le Guennec J-Y, White E (2000) Length-tension relationships of subepicardial and sub-endocardial single ventricular myocytes from rat to ferret hearts. J Mol Cell Cardiol 32:735–744

    Article  PubMed  CAS  Google Scholar 

  3. Chiu YC, Ballou EW, Ford LE (1987) Force, velocity, and power changes during normal and potentiated contractions of cat papillary muscle. Circ Res 60:446–458

    PubMed  CAS  Google Scholar 

  4. Colson BA, Bekyarova T, Fitzsimons DP, Irving TC, Moss RL (2007) Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding-C. J Mol Biol 367:36–41

    Article  PubMed  CAS  Google Scholar 

  5. Colson BA, Bekyarova T, Locher MR, Fitzsimons DP, Irving TC, Moss RL (2008) Protein kinase A-mediated phosphorylation of cMyBP-C increases proximity of myosin heads to actin in resting myocardium. Circulation Research 103:244

    Article  PubMed  CAS  Google Scholar 

  6. Daniels M, Noble MIM, Ter Keurs HEDJ, Wohlfart B (1984) Velocity of sarcomere shortening in rat cardiac muscle: relationship to force, sarcomere length, calcium and time. J Physiol 355:367–381

    PubMed  CAS  Google Scholar 

  7. De Tombe PP, ter Keurs EDJ (1992) An internal viscous element limits unloaded velocity of sarcomere shortening in rat cardiac trabeculae. J Physiol 454:619–642

    PubMed  Google Scholar 

  8. Edman KAP (1979) The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibers. J Physiol 291:143–159

    PubMed  CAS  Google Scholar 

  9. Endoh M, Blinks JR (1988) Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through- and ß-adrenoceptors. Circ Res 62:247–265

    PubMed  CAS  Google Scholar 

  10. Fabiato A, Fabiato F (1975) Dependence of the contractile activation of skinned cardiac cells on the sarcomere length. Nature 256:54–56

    Article  PubMed  CAS  Google Scholar 

  11. Ford LE (1991) Mechanical manifestations of activation of cardiac muscle. Circ Res 68:621–637

    PubMed  CAS  Google Scholar 

  12. Ford LE, Huxley AF, Simmons RM (1985) Tension transients during steady shortening of frog muscle fibres. J Physiol 361:131–150

    PubMed  CAS  Google Scholar 

  13. Ford LE, Nakagawa K, Desper J, Seow CY (1991) Effect of osmotic compression on force-velocity properties of glycerinated rabbit skeletal muscle cells. J Gen Physiol 97:73–88

    Article  PubMed  CAS  Google Scholar 

  14. Fuchs F, Martyn DA (2005) Length-dependent Ca2+ activation in cardiac muscle: some remaining questions. J Muscle Res Cell Motil 26:199–212

    Article  PubMed  CAS  Google Scholar 

  15. Gordon AM, Huxley AF, Julian FJ (1966) The variation in isometric tension with sarcomere length in vertebrate muscle fibers. J Physiol 184:170–192

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Granzier HLM, Burns DH, Pollack GH (1989) Sarcomere length dependence of the force-velocity relation in single frog muscle fibers. Biophys J 55:499–507

    Article  PubMed  CAS  Google Scholar 

  18. Guyton AC, Jones CE, Coleman TG (1973) Circulatory physiology: cardiac output and its regulation. Saunders, Philadelphia

    Google Scholar 

  19. Hanft LM, McDonald KS (2009) Sarcomere length dependence of power output is increased after PKA treatment in rat cardiac myocytes. Am J Physiol 296:H1524–H1531

    CAS  Google Scholar 

  20. Hanft LM, McDonald KS (2010) Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres. J Physiol 588:2891–2903

    Article  PubMed  CAS  Google Scholar 

  21. Hanft LM, McDonald KS (2010) Determinants of loaded shortening in rat cardiac myocytes, 2010 biophysical society meetings abstract

  22. Huxley AF (1957) Muscle structure and theories of contraction. Prog Biophys Biophys Chem 7:255–318

    PubMed  CAS  Google Scholar 

  23. Julian FJ (1971) The effect of calcium on the force-velocity relation of briefly glycerinated frog muscle fibres. J Physiol 218:117–145

    PubMed  CAS  Google Scholar 

  24. Kentish JC, ter Keurs HEDJ, Noble MI, Ricciardi I, Schouten VJA (1983) The relationships between force, [Ca2+] and sarcomere length in skinned trabeculae from rat ventricle. J Physiol 345:24P

    Google Scholar 

  25. Konhilas JP, Irving TC, Wolska BM, Jweied EE, Martin AF, Solaro RJ, deTombe PP (2003) Troponin I in the murine myocardium: influence on length-dependent activation and interfilament spacing. J Physiol 547:951–961

    Article  PubMed  CAS  Google Scholar 

  26. Korte FS, McDonald KS (2007) Sarcomere length dependence of rat skinned cardiac myocyte mechanical properties: dependence on myosin heavy chain. J Physiol 581:725–739

    Article  PubMed  Google Scholar 

  27. Korte FS, McDonald KS, Harris SP, Moss RL (2003) Loaded shortening, power output, and rate of force redevelopment are increased with knockout of cardiac myosin binding protein-C. Circ Res 93:752–758

    Article  PubMed  CAS  Google Scholar 

  28. Luther PK, Bennett PM, Knupp C, Craig R, Padron R, Harris SP, Patel J, Moss RL (2008) Understanding the organisation and role of myosin binding protein C in normal striated muscle by comparison with MyBP-C knockout cardiac muscle. J Mol Biol 384:60–72

    Article  PubMed  CAS  Google Scholar 

  29. Martyn DA, Rondinone JF, Huntsman LL (1983) Myocardial segment velocity at a low load: time, length, and calcium dependence. Am J Physiol 13:H708–H714

    Google Scholar 

  30. McDonald KS (2000) Ca2+ dependence of loaded shortening in rat skinned cardiac myocytes and skeletal muscle fibers. J Physiol 525:169–181

    Article  PubMed  CAS  Google Scholar 

  31. McDonald KS, Moss RL (2000) Strongly binding myosin cross-bridges regulate loaded shortening and power output in cardiac myocytes. Circ Res 87:768–773

    PubMed  CAS  Google Scholar 

  32. McKillop DF, Geeves MA (1993) Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. Biophys J 65:693–701

    Article  PubMed  CAS  Google Scholar 

  33. Moss RL (1992) Ca2+ regulation of mechanical properties of striated muscle: mechanistic studies using extraction and replacement of regulatory proteins. Circ Res 70:865–884

    PubMed  CAS  Google Scholar 

  34. Moss RL, Allen JD, Greaser ML (1986) Effects of partial extraction of troponin complex upon the tension-pCa relation in rabbit skeletal muscle. Further evidence that tension development involves cooperative effects within the thin filament. J Gen Physiol 87:761–774

    Article  PubMed  CAS  Google Scholar 

  35. Piazzesi G, Reconditi M, Linari M, Lucii L, Bianco P, Brunello E, Decostre V, Stewart A, Gore DB, Irving TC, Irving M, Lombardi V (2007) Skeletal muscle performance determined by modulation of number of myosin motors rather than motor force or stroke size. Cell 131:784–795

    Article  PubMed  CAS  Google Scholar 

  36. Podolin RA, Ford LE (1983) The influence of calcium on shortening velocity of skinned frog muscle cells. J Muscle Res Cell Motil 4:263–282

    Article  PubMed  CAS  Google Scholar 

  37. Podolsky RJ, Teichholz LE (1970) The relation between calcium and contraction kinetics in skinned muscle fibres. J Physiol 211:19–35

    PubMed  CAS  Google Scholar 

  38. Sarnoff SJ (1955) Myocardial contractility as described by ventricular function curves; observations on Starling’s law of the heart. Physiol Rev 35:107–122

    PubMed  CAS  Google Scholar 

  39. Sweitzer NK, Moss RL (1993) Determinants of loaded shortening velocity in single cardiac myocytes permeabilized with alpha-hemolysin. Circ Res 73:1150–1162

    PubMed  CAS  Google Scholar 

  40. ter Keurs HE, Rijnsburger WH, van Heuningen R, Nagelsmit MJ (1980) Tension development and sarcomere length in rat cardiac trabeculae. Evidence of length-dependent activation. Circ Res 46:703–714

    PubMed  Google Scholar 

  41. Tobacman L (1996) Thin filament-mediated regulation of cardiac contraction. Annu Rev Physiol 58:447–481

    Article  PubMed  CAS  Google Scholar 

  42. van der Velden J, de Jong JW, Owen VJ, Burton PBJ, Stienen GJM (2000) Effect of protein kinase A on calcium sensitivity of force and its sarcomere length dependence in human cardiomyocytes. Cardiovasc Res 46:487–495

    Article  PubMed  Google Scholar 

  43. Vibert P, Craig R, Lehman W (1997) Steric-model for activation of muscle thin filaments. J Mol Biol 266:8–14

    Article  PubMed  CAS  Google Scholar 

  44. Wahr PA, Metzger JM (1999) Role of Ca2+ and cross-bridges in skeletal muscle thin filament activation probed by Ca2+ sensitizers. Biophys J 76:2166–2176

    Article  PubMed  CAS  Google Scholar 

  45. Wolska BM, Stojanovic MO, Luo W, Kranias EG, Solaro RJ (1996) Effect of ablation of phospholamban on dynamics of cardiac myocyte contraction and intracellular calcium. Am J Physiol 271:C391–C397

    PubMed  CAS  Google Scholar 

  46. Xu C, Craig R, Tobacman L, Horowitz R, Lehman W (1999) Tropomyosin positions in regulated thin filaments revealed by cryoelectron microscopy. Biophys J 77:985–992

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Special acknowledgment is given to Dr. Laurin M. Hanft for helpful comments regarding all aspects of the manuscript and with preparation of the figures.

Author information

Authors and Affiliations

  1. Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, MA 415 Medical Sciences Building, Columbia, MO, 65212, USA

    Kerry S. McDonald

Authors
  1. Kerry S. McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kerry S. McDonald.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDonald, K.S. The interdependence of Ca2+ activation, sarcomere length, and power output in the heart. Pflugers Arch - Eur J Physiol 462, 61–67 (2011). https://doi.org/10.1007/s00424-011-0949-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-011-0949-y

Keywords

Search

Navigation