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Non-crossbridge forces in activated striated muscles: a titin dependent mechanism of regulation?

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Abstract

When skeletal muscles are stretched during activation in the absence of myosin-actin interactions, the force increases significantly. The force remains elevated throughout the activation period. The mechanism behind this non-crossbridge force, referred to as static tension, is unknown and generates debate in the literature. It has been suggested that the static tension is caused by Ca2+-induced changes in the properties of titin molecules that happens during activation and stretch, but a comprehensive evaluation of such possibility is still lacking. This paper reviews the general characteristics of the static tension, and evaluates the proposed mechanism by which titin may change the force upon stretch. Evidence is presented suggesting that an increase in intracellular Ca2+ concentration leads to Ca2+ binding to the PEVK region of titin. Such binding increases titin stiffness, which increases the overall sarcomere stiffness and causes the static tension. If this form of Ca2+-induced increase in titin stiffness is confirmed in future studies, it may have large implications for understating of the basic mechanisms of muscle contraction.

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Acknowledgments

We would like to thank Prof. Giovanni Cecchi for his significant contributions to the concepts introduced in this paper. The ideas reviewed in this paper results from the work of many investigators; due to space limitations, several references dealing directly or indirectly with the subject were omitted. This research was supported by the Canadian Institutes of Health Research (CIHR), the Natural Science and Engineering Research Council of Canada (NSERC) and University of Florence, Ente Cassa di Risparmio di Firenze (2011.0302) and PRIN 2010-11: Pr. 2010R8JK2X, MIUR, Italy. Felipe S. Leite is a recipient of a CNPq scholarship, Brazil. Anabelle S. Cornachione is funded by FAPESP, Brazil.

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Authors and Affiliations

  1. Department of Kinesiology and Physical Education, McGill University, Montreal, Canada

    Dilson E. Rassier & Felipe S. Leite

  2. Departments of Physiology and Physics, McGill University, Montreal, Canada

    Dilson E. Rassier

  3. Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy

    Marta Nocella, Barbara Colombini & Maria Angela Bagni

  4. Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Anabelle S. Cornachione

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  1. Dilson E. Rassier
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  2. Felipe S. Leite
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  3. Marta Nocella
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  4. Anabelle S. Cornachione
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  5. Barbara Colombini
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  6. Maria Angela Bagni
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Correspondence to Dilson E. Rassier.

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Rassier, D.E., Leite, F.S., Nocella, M. et al. Non-crossbridge forces in activated striated muscles: a titin dependent mechanism of regulation?. J Muscle Res Cell Motil 36, 37–45 (2015). https://doi.org/10.1007/s10974-014-9397-6

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  • DOI: https://doi.org/10.1007/s10974-014-9397-6

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