Skip to main content

Advertisement

Log in

Optogenetic control of heart muscle in vitro and in vivo

  • Brief Communication
  • Published:

From Nature Methods

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

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.

Similar content being viewed by others

References

  1. Wikswo, J.P. Jr., Lin, S.F. & Abbas, R.A. Biophys. J. 69, 2195–2210 (1995).

    Article  CAS  Google Scholar 

  2. Merrill, D.R., Bikson, M. & Jefferys, J.G. J. Neurosci. Methods 141, 171–198 (2005).

    Article  Google Scholar 

  3. Gillis, A.M., Fast, V.G., Rohr, S. & Kleber, A.G. Circ. Res. 79, 676–690 (1996).

    Article  CAS  Google Scholar 

  4. Knisley, S.B., Trayanova, N. & Aguel, F. Biophys. J. 77, 1404–1417 (1999).

    Article  CAS  Google Scholar 

  5. Nagel, G. et al. Proc. Natl. Acad. Sci. USA 100, 13940–13945 (2003).

    Article  CAS  Google Scholar 

  6. Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Nat. Neurosci. 8, 1263–1268 (2005).

    CAS  Google Scholar 

  7. Nagel, G. et al. Curr. Biol. 15, 2279–2284 (2005).

    Article  CAS  Google Scholar 

  8. Gradinaru, V. et al. J. Neurosci. 27, 14231–14238 (2007).

    Article  CAS  Google Scholar 

  9. Kolossov, E. et al. J. Exp. Med. 203, 2315–2327 (2006).

    Article  CAS  Google Scholar 

  10. Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T. & Nishimune, Y. FEBS Lett. 407, 313–319 (1997).

    Article  CAS  Google Scholar 

  11. Maltsev, V.A., Wobus, A.M., Rohwedel, J., Bader, M. & Hescheler, J. Circ. Res. 75, 233–244 (1994).

    Article  CAS  Google Scholar 

  12. Roell, W. et al. Nature 450, 819–824 (2007).

    Article  CAS  Google Scholar 

  13. Salama, G. et al. J. Membr. Biol. 208, 125–140 (2005).

    Article  CAS  Google Scholar 

  14. O'Rourke, B. et al. Circ. Res. 84, 562–570 (1999).

    Article  CAS  Google Scholar 

  15. Bers, D.M. Annu. Rev. Physiol. 70, 23–49 (2008).

    Article  CAS  Google Scholar 

  16. Wobus, A.M., Wallukat, G. & Hescheler, J. Differentiation 48, 173–182 (1991).

    Article  CAS  Google Scholar 

  17. Sasse, P. et al. J. Gen. Physiol. 130, 133–144 (2007).

    Article  CAS  Google Scholar 

  18. George, S.H. et al. Proc. Natl. Acad. Sci. USA 104, 4455–4460 (2007).

    Article  CAS  Google Scholar 

  19. Nagy, A. et al. Development 110, 815–821 (1990).

    CAS  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

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.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.1512

  • Springer Nature America, Inc.

This article is cited by

Navigation