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Pflügers Archiv

, Volume 449, Issue 6, pp 505–517 | Cite as

Sarcomeric determinants of striated muscle relaxation kinetics

  • Corrado Poggesi
  • Chiara Tesi
  • Robert Stehle
Invited Review

Abstract

Ca2+ is the primary regulator of force generation by cross-bridges in striated muscle activation and relaxation. Relaxation is as necessary as contraction and, while the kinetics of Ca2+-induced force development have been investigated extensively, those of force relaxation have been both studied and understood less well. Knowledge of the molecular mechanisms underlying relaxation kinetics is of special importance for understanding diastolic function and dysfunction of the heart. A number of experimental models, from whole muscle organs and intact muscle fibres down to single myofibrils, have been used to explore the cascade of kinetic events leading to mechanical relaxation. By using isolated myofibrils and fast solution switching techniques we can distinguish the sarcomeric mechanisms of relaxation from those of myoplasmic Ca2+ removal. There is strong evidence that cross-bridge mechanics and kinetics are major determinants of the time course of striated muscle relaxation whilst thin filament inactivation kinetics and cooperative activation of thin filament by cycling, force-generating cross-bridges do not significantly limit the relaxation rate. Results in myofibrils can be explained well by a simple two-state model of the cross-bridge cycle in which the apparent rate of the force generating transition is modulated by fast, Ca2+-dependent equilibration between off- and on-states of actin. Inter-sarcomere dynamics during the final rapid phase of full force relaxation are responsible for deviations from this simple model.

Keywords

Muscle relaxation Thin filament regulation Calcium activation Cross-bridge kinetics Force generation 

Notes

Acknowledgements

The authors gratefully acknowledge Drs. Alexandra Belus, Ulrich H.K. Decking, Martina Krüger, Gabriele Pfitzer, Nicoletta Piroddi, Lucia Pizza and Pieter P. de Tombe (UIC, Chicago) for sharing experimental results. They are also grateful to Drs. Earl Homsher (UCLA, Los Angeles) and Phil W. Brandt (Columbia University, New York) for many stimulating discussions and comments on the subject and to Alessandro Aiazzi, Mario Dolfi, and Adrio Vannucchi (University of Florence) for technical assistance. This work was partially supported by MIUR (COFIN 2002) and DFG (SFB612-A2). The financial supports of Telethon-Italy (grant # GGP02428), EU (HPRN-CT-2000-00091), and the Medical Faculty of the University of Cologne (Köln Fortune # 36/2003) are also gratefully acknowledged.

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Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  1. 1.Dipartimento di Scienze FisiologicheUniversità di FirenzeFlorenceItaly
  2. 2.Institute of Vegetative PhysiologyUniversity of CologneCologneGermany

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