Skip to main content
SpringerLink
Log in

Myosin Heavy Chain Isoforms Modulate Motor Function of Cardiac Myosin by Changing Crossbridge Kinetics

  • Chapter
Pathophysiology of Cardiovascular Disease

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 10))

  • 302 Accesses

Summary

In mammalian hearts, there are two myosin heavy chain (MHC) isoforms, fasttype α-MHC and slow-type β-MHC, and the isoform composition changes in response to mechanical load. In human atria and rodent ventricles, isoform composition shifts from α-to β-MHC under pressure overload. Since α-MHC is related with higher ATPase activity and higher velocity of muscle shortening compared to β-MHC, the redistribution towards β-MHC could be adaptive response to increased mechanical load for better economy. To dissect the molecular mechanism underlying the higher economy of β-MHC, we purified V1 (homodimer of α-MHC) and V3 (homodimer of β-MHC) myosins from rat ventricles and characterized the functional differences in vitro. Both Ca2+-activated ATPase activity and actin filament velocity (VEL) in the in vitro motility assay were twice higher in V1 compared to V3. Ensemble force generated by several myosin molecules was measured with a laser trap. Isometric force per unit length of actin filament, an index of average force of several myosin molecules and time-averaged force of an individual molecule (Fave), was similar between V1 and V3. Displacement under low load and isometric force generated by a single (or a very small number of) myosin molecule(s) were determined by reducing the number of myosin molecules interacting with actin filaments. Both unitary displacement and unitary force were equal between these myosins. Notably, however, the event duration was significantly longer in V3 under both low load and isometric condition compared to V1. Assuming the two-state model of crossbridge, these results suggest that V3 may have proportionally slower kinetics in both attachment and detachment of the crossbridge, which can explain the similar Fave. Importantly, however, to maintain equal level of isometric force, V3 may hydrolyze less number of ATP molecules and thus have better economy than V1.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hoh JFY, McGrath PA, Hale PT. 1978. Electrophoretic analysis of multiple forms of rat cardiac myosin: effects of hypophysectomy and thyroxine replacement. J Mol Cell Cardiol 10: 1053–1076.

    Article  PubMed  CAS  Google Scholar 

  2. Schwartz K, Lecarpentier Y, Martin JL, Lompre AM, Mercadier JJ, Swynghedauw B. 1981. Myosin isozymic distribution correlates with speed of myocardial contraction. J Mol Cell Cardiol 13:1071–1075.

    Article  PubMed  CAS  Google Scholar 

  3. Pagani ED, Julian FJ. 1984. Rabbit papillary muscle myosin isozymes and the velocity of muscle shortening. Circ Res 54:586–594.

    Article  PubMed  CAS  Google Scholar 

  4. Barany M. 1967. ATPase activity associated with the speed of muscle shortening. J Gen Physiol 50S:197–218.

    Article  Google Scholar 

  5. Alpert NR, Mulieri LA. 1982. Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. Circ Res 50:491–500.

    Article  PubMed  CAS  Google Scholar 

  6. Holubarsch CH, Goulette RP, Litten RZ, Martin BJ, Mulieri LA, Alpert NR. 1985. The economy of force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hyperthyroid rat myocardium. Circ Res 56:78–86.

    Article  PubMed  CAS  Google Scholar 

  7. Hasenfuss G, Mulieri LA, Blanchard EM, Holubarsch C, Leavitt BJ, Ittleman F, Alpert NR. 1991. Energetics of isometric force development in control and volume-overload human myocardium: comparison with animal species. Circ Res 68:836–846.

    Article  PubMed  CAS  Google Scholar 

  8. Sata M, Sugiura S, Yamashita H, Momomura S, Serizawa T. 1993. Dynamic interaction between cardiac myosin isoforms modifies velocity of actomyosin sliding in vitro. Circ Res 73:696–704.

    Article  PubMed  CAS  Google Scholar 

  9. Sugiura S, Kobayakawa N, Momomura S, Chaen S, Omata M, Sugi H. 1996. Different cardiac myosin isoforms exhibit equal force-generating ability in vitro. Biochim Biophys Acta 1273:73–76.

    Article  PubMed  Google Scholar 

  10. Kron SJ, Spudich JA. 1986. Fluorescent actin filaments move on myosin fixed to a glass surface. Proc Natl Acad Sci U S A 83:6272–6276.

    Article  PubMed  CAS  Google Scholar 

  11. Ashkin A. 1992. Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime. Biophys J 61:569–582.

    Article  PubMed  CAS  Google Scholar 

  12. Finer JT, Simmons RM, Spudich JA. 1994. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature 368:113–119.

    Article  PubMed  CAS  Google Scholar 

  13. Guilford WH, Dupuis DE, Kennedy G, Wu J, Patlak JB, Warshaw DM. 1997. Smooth muscle and skeletal muscle myosins produce similar unitary forces and displacement in the laser trap. Biophvs J 72:1006–1021.

    Article  CAS  Google Scholar 

  14. Sugiura S, Kobayakawa N, Fujita H, Yamashita H, Momomura S, Chaen S, Omata M, Sugi H. 1998. Comparison of unitary displacements and forces between 2 cardiac myosin isoforms by the optical trap technique: molecular basis for cardiac adaptation. Circ Res 82:1029–1034.

    Article  PubMed  CAS  Google Scholar 

  15. Harris DE, Work SS, Wright PJC, Alpert NR, Warshaw DM. 1994. Smooth, cardiac, and skeletal muscle myosin force and motion generation assessed by cross-bridge mechanical interaction in vitro. J Muscle Res Cell Motil 15:11–19.

    Article  PubMed  CAS  Google Scholar 

  16. VanBuren P, Harris DE, Alpert NR, Warshaw DM. 1995. Cardiac V1 and V3 myosins differ in their hydrolytic and mechanical activities in vitro. Circ Res 77:439–444.

    Article  Google Scholar 

  17. Palmiter KA, Tyska MJ, Dupuis DE, Alpert NR, Warshaw DM. 1999. Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms. J Physiol 519: 669–678.

    Article  PubMed  CAS  Google Scholar 

  18. Maughan D, Low E, Litten R III, Brayden J, Alpert N. 1979. Calcium-activated muscle from hypertrophied rabbit hearts: mechanical and correlated biochemical changes. Circ Res 44:279–287.

    Article  PubMed  CAS  Google Scholar 

  19. Rupp H. 1981. The adaptive changes in the isoenzyme pattern of myosin from hypertrophied rat myocardium as a result of pressure overload and physiological training. Basic Res Cardiol 76:79–88.

    Article  PubMed  CAS  Google Scholar 

  20. Shibata T, Hunter WC, Sagawa K. 1987. Dynamic stiffness of barium-contractured cardiac muscle with different speeds of contraction. Circ Res 60:770–779.

    Article  PubMed  CAS  Google Scholar 

  21. Loiselle DS, Wendt IR, Hoh JFY. 1982. Energetic consequences of thyroid-modulated shifts in ventricular isomyosin distribution in the rat. J Muscle Res Cell Motil 3:5–23.

    Article  PubMed  CAS  Google Scholar 

  22. Saeki Y, Kako C, Totsuka T, Yanagisawa K. 1987. Mechanical properties and ATPase activity in glycerinated cardiac muscle of hyperthyroid rabbit. Pflugers Arch 408:578–583.

    Article  PubMed  CAS  Google Scholar 

  23. Fitzsimons DP, Patel JR, Moss RL. 1998. Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium. J Physiol 513:171–183.

    Article  PubMed  CAS  Google Scholar 

  24. Metzger JM, Wahr PA, Michele DE, Albayya F, Westfall MV. 1999. Effects of myosin heavy chain isoform switching on Ca2+-activated tension development in single adult cardiac myocytes. Circ Res 84:1310–1317.

    Article  PubMed  CAS  Google Scholar 

  25. Huxley AF. 1957. Muscle structure and theories of contraction. Prog Biophys Biophys Chem 7: 255–317.

    PubMed  CAS  Google Scholar 

  26. Tsuchimochi H, Sugi M, Kuro-o S, Ueda F, Takaku F, Furuta S, Shirai T, Yazaki Y. 1984. Isozymic change in myosin of human atrial myocardium induced by overload: immunohistochemical study using monoclonal antibodies. J Clin Invest 74:662–665.

    Article  PubMed  CAS  Google Scholar 

  27. Mercadier JJ, Bouveret P, Gorza L, Schiaffino S, Clark WA, Zak R, Swynghedauw B, Schwartz K. 1983. Myosin isoenzymes in normal and hypertrophied human ventricular myocardium. Circ Res 53:52–62.

    Article  PubMed  CAS  Google Scholar 

  28. Nakao K, Minobe W, Roden R, Bristow MR, Leinwand LA. 1997. Myosin heavy chain gene expression in human heart failure. J Clin Invest 100:2362–2370.

    Article  PubMed  CAS  Google Scholar 

  29. Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR. 1997. Changes in gene expression in the intact human heart: downregulation of α-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 100:2315–2324.

    Article  PubMed  CAS  Google Scholar 

  30. Miyata S, Minobe W, Bristow MR, Leinwand LA. 2000. Myosin heavy chain isoform expression in the failing and nonfailing human heart. Circ Res 86:386–390.

    Article  PubMed  CAS  Google Scholar 

  31. 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 

  32. Tardiff JC, Hewett TE, Factor SM, Vikstrom KL, Robbins J, Leinwand LA. 2000. Expression of the β(slow)-isoform of the MHC in the adult mouse heart causes dominant-negative functional effects. Am J Physiol 278:H412–H419.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hiroshi Yamashita M.D., Ph.D., Seiryo Sugiura, Hideo Fujita, Soichiro Yasuda & Ryozo Nagai

  2. Department of Physiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, 230-8501, Japan

    Yasutake Saeki

  3. Department of Physiology, School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Haruo Sugi

Authors
  1. Hiroshi Yamashita M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seiryo Sugiura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideo Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Soichiro Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryozo Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasutake Saeki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Haruo Sugi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Yamashita M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

  2. Philipps University of Marburg, Marburg, Germany

    Heinz Rupp PhD (Professor of Medicine) (Professor of Medicine)

  3. Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Aubie Angel MD (Professor of Internal Medicine) (Professor of Internal Medicine)

  4. Division of Stroke & Vascular Disease St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Yamashita, H. et al. (2004). Myosin Heavy Chain Isoforms Modulate Motor Function of Cardiac Myosin by Changing Crossbridge Kinetics. In: Dhalla, N.S., Rupp, H., Angel, A., Pierce, G.N. (eds) Pathophysiology of Cardiovascular Disease. Progress in Experimental Cardiology, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0453-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0453-5_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5084-2

  • Online ISBN: 978-1-4615-0453-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation