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Optogenetic control of heart muscle in vitro and in vivo

Abstract

Electrical stimulation is the standard technique for exploring electrical behavior of heart muscle, but this approach has considerable technical limitations. Here we report expression of the light-activated cation channel channelrhodopsin-2 for light-induced stimulation of heart muscle in vitro and in mice. This method enabled precise localized stimulation and constant prolonged depolarization of cardiomyocytes and cardiac tissue resulting in alterations of pacemaking, Ca2+ homeostasis, electrical coupling and arrhythmogenic spontaneous extrabeats.

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Figure 1: Generation and characterization of ChR2-expressing cardiomyocytes in vitro.
Figure 2: Expression and function of ChR2 in ventricular cardiomyocytes from CAG-ChR2 mice.
Figure 3: Light-induced stimulation of ChR2-expressing hearts in vivo.

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Acknowledgements

We thank K. Deisseroth (Stanford University) for providing the pcDNA3.1/hChR2(H134R)-EYFP plasmid, A. Nagy and M. Gertsenstein (Mount Sinai Hospital, Toronto) for providing the G4 mouse embryonic stem cell line, H. Begerau (University Bonn) for writing the frequency analysis software, and F. Holst and M. Czechowski for technical assistance. This work was supported by grants from the Bonfor program (Medical Faculty, University Bonn) (to T. Bruegmann and P.S.), Deutsche Forschungsgemeinschaft (FL 276/3-3) and European Community Network of Excellence (LSHB-CT-2005-512146).

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Authors

Contributions

T. Bruegmann, B.K.F. and P.S. designed the study and prepared the manuscript. T. Bruegmann, D.M., T. Beiert and P.S. performed experiments and analyzed data. C.J.F. and M.H. generated the transgenic mice.

Corresponding author

Correspondence to Philipp Sasse.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Note 1 (PDF 968 kb)

Supplementary Video 1

Video of a spontaneously beating embryoid body with ChR2-expressing cardiomyocytes. Light stimulation (100 ms, 7.1 mW mm−2) is indicated by a blue box in right upper corner. Recording and display frame rate is 20 frames s−1. (MOV 2673 kb)

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Bruegmann, T., Malan, D., Hesse, M. et al. Optogenetic control of heart muscle in vitro and in vivo. Nat Methods 7, 897–900 (2010). https://doi.org/10.1038/nmeth.1512

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