1. Cell Biology
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An adaptation of astronomical image processing enables characterization and functional 3D mapping of individual sites of excitation-contraction coupling in rat cardiac muscle

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Cite as: eLife 2017;6:e30425 doi: 10.7554/eLife.30425

Abstract

In beating cardiomyocytes, synchronized localized Ca2+ transients from thousands of active excitation-contraction coupling sites (ECC couplons) comprising plasma and sarcoplasmic reticulum membrane calcium channels are important determinants of the heart's performance. Nevertheless, our knowledge about their properties is limited by the lack of appropriate experimental and analysis strategies. We designed CaCLEAN to untangle fundamental characteristics of ECC couplons by combining the astronomer's CLEAN algorithm with known properties of calcium diffusion. CaCLEAN empowers the investigation of fundamental properties of ECC couplons in beating cardiomyocytes without pharmacological interventions. On the nanoscopic level of individual ECC couplons, we reveal their role in the negative amplitude-frequency relationship and b-adrenergic stimulation, including decreasing and increasing firing reliability, respectively. CaCLEAN combined with 3D confocal imaging of beating cardiomyocytes provides a functional 3D map of active ECC couplons (on average 17.000 per myocyte). CaCLEAN will further enlighten remodelling processes of ECC couplons underlying cardiac diseases.

Article and author information

Author details

  1. Qinghai Tian

    Institute for Molecular Cell Biology, Center for Molecular Signaling (PZMS), Saarland University, Homburg/Saar, Germany
    For correspondence
    tian_qhcn@icloud.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Lars Kaestner

    Institute for Molecular Cell Biology, Center for Molecular Signaling (PZMS), Saarland University, Homburg/Saar, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura Schröder

    Institute for Molecular Cell Biology, Center for Molecular Signaling (PZMS), Saarland University, Homburg/Saar, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jia Guo

    Institute for Molecular Cell Biology, Center for Molecular Signaling (PZMS), Saarland University, Homburg/Saar, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Peter Lipp

    Institute for Molecular Cell Biology, Center for Molecular Signaling (PZMS), Saarland University, Homburg/Saar, Germany
    For correspondence
    peter.lipp@uks.eu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-4728-9174

Funding

Deutsche Forschungsgemeinschaft

  • Peter Lipp

Saarland University, Medical Faculty

  • Qinghai Tian
  • Jia Guo

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

Reviewing Editor

  1. Richard S Lewis, Reviewing Editor, Stanford University School of Medicine, United States

Publication history

  1. Received: July 14, 2017
  2. Accepted: November 3, 2017
  3. Accepted Manuscript published: November 14, 2017 (version 1)
  4. Accepted Manuscript updated: November 16, 2017 (version 2)

Copyright

© 2017, Tian 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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