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Optogenetic stimulation of Gs-signaling in the heart with high spatio-temporal precision

Author

Listed:
  • Philipp Makowka

    (University of Bonn)

  • Tobias Bruegmann

    (University of Bonn
    University of Bonn
    University Medical Center)

  • Vanessa Dusend

    (University of Bonn
    University of Bonn)

  • Daniela Malan

    (University of Bonn)

  • Thomas Beiert

    (University of Bonn)

  • Michael Hesse

    (University of Bonn)

  • Bernd K. Fleischmann

    (University of Bonn)

  • Philipp Sasse

    (University of Bonn)

Abstract

The standard technique for investigating adrenergic effects on heart function is perfusion with pharmaceutical agonists, which does not provide high temporal or spatial precision. Herein we demonstrate that the light sensitive Gs-protein coupled receptor JellyOp enables optogenetic stimulation of Gs-signaling in cardiomyocytes and the whole heart. Illumination of transgenic embryonic stem cell-derived cardiomyocytes or of the right atrium of mice expressing JellyOp elevates cAMP levels and instantaneously accelerates spontaneous beating rates similar to pharmacological β-adrenergic stimulation. Light application to the dorsal left atrium instead leads to supraventricular extrabeats, indicating adverse effects of localized Gs-signaling. In isolated ventricular cardiomyocytes from JellyOp mice, we find increased Ca2+ currents, fractional cell shortening and relaxation rates after illumination enabling the analysis of differential Gs-signaling with high temporal precision. Thus, JellyOp expression allows localized and time-restricted Gs stimulation and will provide mechanistic insights into different effects of site-specific, long-lasting and pulsatile Gs activation.

Suggested Citation

  • Philipp Makowka & Tobias Bruegmann & Vanessa Dusend & Daniela Malan & Thomas Beiert & Michael Hesse & Bernd K. Fleischmann & Philipp Sasse, 2019. "Optogenetic stimulation of Gs-signaling in the heart with high spatio-temporal precision," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09322-7
    DOI: 10.1038/s41467-019-09322-7
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    Cited by:

    1. Ahmed Wagdi & Daniela Malan & Udhayabhaskar Sathyanarayanan & Janosch S. Beauchamp & Markus Vogt & David Zipf & Thomas Beiert & Berivan Mansuroglu & Vanessa Dusend & Mark Meininghaus & Linn Schneider , 2022. "Selective optogenetic control of Gq signaling using human Neuropsin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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