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Impact of myocyte strain on cardiac myofilament activation

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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.

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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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Authors and Affiliations

  1. Department of Physiology and Center for Muscle Biology, University of Kentucky, Lexington, KY, USA

    Kenneth S. Campbell

  2. Department of Physiology, MS508 Chandler Medical Center, 800 Rose Street, Lexington, KY, 40536-0298, USA

    Kenneth S. Campbell

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Correspondence to Kenneth S. Campbell.

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Campbell, K.S. Impact of myocyte strain on cardiac myofilament activation. Pflugers Arch - Eur J Physiol 462, 3–14 (2011). https://doi.org/10.1007/s00424-011-0952-3

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  • DOI: https://doi.org/10.1007/s00424-011-0952-3

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