Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle

  1. Xuemeng Zhang
  2. Thomas Kampourakis
  3. Ziqian Yan
  4. Ivanka Sevrieva
  5. Malcolm Irving
  6. Yin-Biao Sun  Is a corresponding author
  1. King's College London, United Kingdom

Abstract

The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.

Article and author information

Author details

  1. Xuemeng Zhang

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas Kampourakis

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ziqian Yan

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ivanka Sevrieva

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Malcolm Irving

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Yin-Biao Sun

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    For correspondence
    yin-biao.sun@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4992-8198

Funding

British Heart Foundation (FS/15/1/31071)

  • Yin-Biao Sun

British Heart Foundation (FS/09/001/26329)

  • Yin-Biao Sun

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was carried out in accordance with Schedule 1 of the UK Animal (Scientific Procedures) Act 1986, as approved by the King's College London Ethical Review Process committee.

Reviewing Editor

  1. James Spudich, Stanford University School of Medicine, United States

Publication history

  1. Received: December 8, 2016
  2. Accepted: February 20, 2017
  3. Accepted Manuscript published: February 23, 2017 (version 1)
  4. Version of Record published: March 24, 2017 (version 2)

Copyright

© 2017, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xuemeng Zhang
  2. Thomas Kampourakis
  3. Ziqian Yan
  4. Ivanka Sevrieva
  5. Malcolm Irving
  6. Yin-Biao Sun
(2017)
Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
eLife 6:e24081.
https://doi.org/10.7554/eLife.24081

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