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High ionic strength depresses muscle contractility by decreasing both force per cross-bridge and the number of strongly attached cross-bridges

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Abstract

An increase in ionic strength (IS) lowers Ca2+ activated tension in muscle fibres, however, its molecular mechanism is not well understood. In this study, we used single rabbit psoas fibres to perform sinusoidal analyses. During Ca2+ activation, the effects of ligands (ATP, Pi, and ADP) at IS ranging 150–300 mM were studied on three rate constants to characterize elementary steps of the cross-bridge cycle. The IS effects were studied because a change in IS modifies the inter- and intra-molecular interactions, hence they may shed light on the molecular mechanisms of force generation. Both the ATP binding affinity (K 1) and the ADP binding affinity (K 0) increased to 2–3x, and the Pi binding affinity (K 5) decreased to 1/2, when IS was raised from 150 to 300 mM. The effect on ATP/ADP can be explained by stereospecific and hydrophobic interaction, and the effect on Pi can be explained by the electrostatic interaction with myosin. The increase in IS increased cross-bridge detachment steps (k 2 and k −4), indicating that electrostatic repulsion promotes these steps. However, IS did not affect attachment steps (k −2 and k 4). Consequently, the equilibrium constant of the detachment step (K 2) increased by ~100 %, and the force generation step (K 4) decreased by ~30 %. These effects together diminished the number of force-generating cross-bridges by 11 %. Force/cross-bridge (T 56) decreased by 26 %, which correlates well with a decrease in the Debye length that limits the ionic atmosphere where ionic interactions take place. We conclude that the major effect of IS is a decrease in force/cross-bridge, but a decrease in the number of force generating cross-bridge also takes place. The stiffness during rigor induction did not change with IS, demonstrating that in-series compliance is not much affected by IS.

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Acknowledgments

This work was supported by grants from the National Institutes of Health HL070041 (MK), and The American Heart Association 13GRNT16810043 (MK). This study was carried out during Dr. Anzel Bahadir’s visit to The University of Iowa with a scholarship (82444403-299-1926) funded by Higher Educational Council of Turkey. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the funding organizations.

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The authors have no conflicts of interests.

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Authors and Affiliations

  1. School of Nursing, Soochow University, Suzhou, 215006, Jiangsu, China

    Li Wang

  2. Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    Li Wang & Masataka Kawai

  3. Department of Biophysics, Faculty of Medicine, Duzce University, Konuralp Campus, 81620, Duzce, Turkey

    Anzel Bahadir

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  1. Li Wang
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  2. Anzel Bahadir
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Correspondence to Masataka Kawai.

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Wang, L., Bahadir, A. & Kawai, M. High ionic strength depresses muscle contractility by decreasing both force per cross-bridge and the number of strongly attached cross-bridges. J Muscle Res Cell Motil 36, 227–241 (2015). https://doi.org/10.1007/s10974-015-9412-6

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  • DOI: https://doi.org/10.1007/s10974-015-9412-6

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