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Photochemical tools for remote control of ion channels in excitable cells

Nature Chemical Biology volume 1, pages 360–365 (2005)Cite this article

Abstract

Various strategies have been developed recently for imparting light sensitivity onto normally insensitive cells. These include expression of natural photosensitive proteins, photolysis of caged agonists of native cell surface receptors and photoswitching of isomerizable tethered ligands that act on specially engineered ion channels and receptor targets. The development of chemical tools for optically stimulating or inhibiting signaling proteins has particular relevance for the nervous system, where precise, noninvasive control is an experimental and medical necessity.

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Figure 1: Light switches for cellular control.
Figure 2: Photolabile protecting groups in caged neurotransmitters.
Figure 3: SPARK, a light-activated K+ channel.
Figure 4: Light opens and closes SPARK channels and controls neuronal firing.

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References

  1. Goeldner, M. & Givens, R. Dynamic Studies in Biology: Phototriggers, Photoswitches and Caged Biomolecules (Wiley-VCH, Weinheim, Germany, 2005).

    Book  Google Scholar 

  2. Briggs, W.R. & Spudich, J.L. Handbook of Photosensory Receptors (Wiley-VCH, Weinheim, Germany, 2005).

    Book  Google Scholar 

  3. Minke, B. & Cook, B. TRP channel proteins and signal transduction. Physiol. Rev. 82, 429–472 (2002).

    Article  CAS  Google Scholar 

  4. Zemelman, B.V., Lee, G.A., Ng, M. & Miesenbock, G. Selective photostimulation of genetically chARGed neurons. Neuron 33, 15–22 (2002).

    Article  CAS  Google Scholar 

  5. Melyan, Z., Tarttelin, E.E., Bellingham, J., Lucas, R.J. & Hankins, M.W. Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433, 741–745 (2005).

    Article  CAS  Google Scholar 

  6. Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).

    Article  CAS  Google Scholar 

  7. Kaplan, J.H., Forbush, B., III & Hoffman, J.F. Rapid photolytic release of adenosine 5′-triphosphate from a protected analogue: utilization by the Na:K pump of human red blood cell ghosts. Biochemistry 17, 1929–1935 (1978).

    Article  CAS  Google Scholar 

  8. McCray, J.A., Herbette, L., Kihara, T. & Trentham, D.R. A new approach to time-resolved studies of ATP-requiring biological systems; laser flash photolysis of caged ATP. Proc. Natl. Acad. Sci. USA 77, 7237–7241 (1980).

    Article  CAS  Google Scholar 

  9. Engels, J. & Schlaeger, E.J. Synthesis, structure, and reactivity of adenosine cyclic 3′,5′-phosphate benzyl triesters. J. Med. Chem. 20, 907–911 (1977).

    Article  CAS  Google Scholar 

  10. Nerbonne, J.M., Richard, S., Nargeot, J. & Lester, H.A. New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations. Nature 310, 74–76 (1984).

    Article  CAS  Google Scholar 

  11. Nargeot, J., Nerbonne, J.M., Engels, J. & Lester, H.A. Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP. Proc. Natl. Acad. Sci. USA 80, 2395–2399 (1983).

    Article  CAS  Google Scholar 

  12. Walker, J.W., McCray, J.A. & Hess, G.P. Photolabile protecting groups for an acetylcholine receptor ligand. Synthesis and photochemistry of a new class of o-nitrobenzyl derivatives and their effects on receptor function. Biochemistry 25, 1799–1805 (1986).

    Article  CAS  Google Scholar 

  13. Nerbonne, J.M. Caged compounds: tools for illuminating neuronal responses and connections. Curr. Opin. Neurobiol. 6, 379–386 (1996).

    Article  CAS  Google Scholar 

  14. Callaway, E.M. & Yuste, R. Stimulating neurons with light. Curr. Opin. Neurobiol. 12, 587–592 (2002).

    Article  CAS  Google Scholar 

  15. Wieboldt, R. et al. Photolabile precursors of glutamate: synthesis, photochemical properties, and activation of glutamate receptors on a microsecond time scale. Proc. Natl. Acad. Sci. USA 91, 8752–8756 (1994).

    Article  CAS  Google Scholar 

  16. Katz, L.C. & Dalva, M.B. Scanning laser photostimulation: a new approach for analyzing brain circuits. J. Neurosci. Methods 54, 205–218 (1994).

    Article  CAS  Google Scholar 

  17. Callaway, E.M. & Katz, L.C. Photostimulation using caged glutamate reveals functional circuitry in living brain slices. Proc. Natl. Acad. Sci. USA 90, 7661–7665 (1993).

    Article  CAS  Google Scholar 

  18. Denk, W. Two-photon scanning photochemical microscopy: mapping ligand-gated ion channel distributions. Proc. Natl. Acad. Sci. USA 91, 6629–6633 (1994).

    Article  CAS  Google Scholar 

  19. Furuta, T. et al. Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis. Proc. Natl. Acad. Sci. USA 96, 1193–1200 (1999).

    Article  CAS  Google Scholar 

  20. Matsuzaki, M. et al. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat. Neurosci. 4, 1086–1092 (2001).

    Article  CAS  Google Scholar 

  21. Canepari, M., Nelson, L., Papageorgiou, G., Corrie, J.E. & Ogden, D. Photochemical and pharmacological evaluation of 7-nitroindolinyl-and 4-methoxy-7-nitroindolinyl-amino acids as novel, fast caged neurotransmitters. J. Neurosci. Methods 112, 29–42 (2001).

    Article  CAS  Google Scholar 

  22. Pettit, D.L., Wang, S.S., Gee, K.R. & Augustine, G.J. Chemical two-photon uncaging: a novel approach to mapping glutamate receptors. Neuron 19, 465–471 (1997).

    Article  CAS  Google Scholar 

  23. Wang, S.S., Khiroug, L. & Augustine, G.J. Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. Proc. Natl. Acad. Sci. USA 97, 8635–8640 (2000).

    Article  CAS  Google Scholar 

  24. Zemelman, B.V., Nesnas, N., Lee, G.A. & Miesenbock, G. Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons. Proc. Natl. Acad. Sci. USA 100, 1352–1357 (2003).

    Article  CAS  Google Scholar 

  25. Slimko, E.M., McKinney, S., Anderson, D.J., Davidson, N. & Lester, H.A. Selective electrical silencing of mammalian neurons in vitro by the use of invertebrate ligand-gated chloride channels. J. Neurosci. 22, 7373–7379 (2002).

    Article  CAS  Google Scholar 

  26. Lechner, H.A., Lein, E.S. & Callaway, E.M. A genetic method for selective and quickly reversible silencing of mammalian neurons. J. Neurosci. 22, 5287–5290 (2002).

    Article  CAS  Google Scholar 

  27. Sigworth, F.J. Voltage gating of ion channels. Q. Rev. Biophys. 27, 1–40 (1994).

    Article  CAS  Google Scholar 

  28. Yellen, G. The voltage-gated potassium channels and their relatives. Nature 419, 35–42 (2002).

    Article  CAS  Google Scholar 

  29. Banghart, M., Borges, K., Isacoff, E., Trauner, D. & Kramer, R.H. Light-activated ion channels for remote control of neuronal firing. Nat. Neurosci. 7, 1381–1386 (2004).

    Article  CAS  Google Scholar 

  30. Bayley, H. & Knowles, J.R. Photoaffinity labeling. Methods Enzymol. 46, 69–114 (1977).

    Article  CAS  Google Scholar 

  31. Heginbotham, L., Lu, Z., Abramson, T. & MacKinnon, R. Mutations in the K+ channel signature sequence. Biophys. J. 66, 1061–1067 (1994).

    Article  CAS  Google Scholar 

  32. Forber, C.L., Kelusky, E.C., Bunce, N.J. & Zerner, M.C. Electronic spectra of cis- and trans-azobenzenes: consequences of ortho substitution. J. Am. Chem. Soc. 107, 5884–5890 (1985).

    Article  CAS  Google Scholar 

  33. Lester, H.A. & Nerbonne, J.M. Physiological and pharmacological manipulations with light flashes. Annu. Rev. Biophys. Bioeng. 11, 151–175 (1982).

    Article  CAS  Google Scholar 

  34. Brejc, K. et al. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411, 269–276 (2001).

    Article  CAS  Google Scholar 

  35. Nanao, M.H., Green, T., Stern-Bach, Y., Heinemann, S.F. & Choe, S. Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid. Proc. Natl. Acad. Sci. USA 102, 1708–1713 (2005).

    Article  CAS  Google Scholar 

  36. Flint, D.G., Kumita, J.R., Smart, O.S. & Woolley, G.A. Using an azobenzene cross-linker to either increase or decrease peptide helix content upon trans-to-cis photoisomerization. Chem. Biol. 9, 391–397 (2002).

    Article  CAS  Google Scholar 

  37. Kumita, J.R., Flint, D.G., Woolley, G.A. & Smart, O.S. Achieving photo-control of protein conformation and activity: producing a photo-controlled leucine zipper. Faraday Discuss. 122, 89–103 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by a Laboratory Directed Research and Development (LDRD) grant from Lawrence Berkeley National Laboratory (R.K and D.T.) and grants from the National Institutes of Health (R.K.).

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, 142 Life Sciences Addition, University of California, Berkeley, Berkeley, 94720, California, USA

    Richard H Kramer & James J Chambers

  2. Department of Chemistry, 602 Latimer Hall, University of California, Berkeley, Berkeley, 94720, California, USA

    Dirk Trauner

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Kramer, R., Chambers, J. & Trauner, D. Photochemical tools for remote control of ion channels in excitable cells. Nat Chem Biol 1, 360–365 (2005). https://doi.org/10.1038/nchembio750

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