Impact of myocyte strain on cardiac myofilament activation

Invited Review

Abstract

When cardiac myocytes are stretched by a longitudinal strain, they develop proportionally more active force at a given sub-maximal Ca2+ concentration than they did at the shorter length. This is known as length-dependent activation. It is one of the most important contributors to the Frank–Starling relationship, a critical part of normal cardiovascular function. Despite intense research efforts, the mechanistic basis of the Frank–Starling relationship remains unclear. Potential mechanisms involving myofibrillar lattice spacing, titin-based effects, and cooperative activation have all been proposed. This review summarizes some of these mechanisms and discusses two additional potential theories that reflect the effects of localized strains that occur within and between half-sarcomeres. The main conclusion is that the Frank–Starling relationship is probably the integrated result of many interacting molecular mechanisms. Multiscale computational modeling may therefore provide the best way of determining the key processes that underlie length-dependent activation and their relative strengths.

Keywords

Muscle Ventricular myocyte Ventricle Myosin Myofilament Myocardial contractility Muscle stretch Muscle mechanics 

Notes

Acknowledgments

This work was supported by NIH HL090749 to KSC and the University of Kentucky Research Challenge Trust Fund. The author thanks Stuart G. Campbell and Premi Shekar (both University of Kentucky) for helpful discussions.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Physiology and Center for Muscle BiologyUniversity of KentuckyLexingtonUSA
  2. 2.Department of PhysiologyMS508 Chandler Medical CenterLexingtonUSA

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