Photochemical control of endogenous ion channels and cellular excitability

Doris L. Fortin, Matthew R. Banghart, Timothy W. Dunn, Katharine Borges, Daniel A. Wagenaar, Quentin Gaudry, Movses H. Karakossian, Thomas S. Otis, William B. Kristan, Dirk Trauner, Richard H. Kramer

Research output: Contribution to journalArticle

Abstract

Light-activated ion channels provide a precise and noninvasive optical means for controlling action potential firing, but the genes encoding these channels must first be delivered and expressed in target cells. Here we describe a method for bestowing light sensitivity onto endogenous ion channels that does not rely on exogenous gene expression. The method uses a synthetic photoisomerizable small molecule, or photoswitchable affinity label (PAL), that specifically targets K+ channels. PALs contain a reactive electrophile, enabling covalent attachment of the photoswitch to naturally occurring nucleophiles in K+ channels. Ion flow through PAL-modified channels is turned on or off by photoisomerizing PAL with different wavelengths of light. We showed that PAL treatment confers light sensitivity onto endogenous K+ channels in isolated rat neurons and in intact neural structures from rat and leech, allowing rapid optical regulation of excitability without genetic modification.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalNature methods
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2008

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fortin, D. L., Banghart, M. R., Dunn, T. W., Borges, K., Wagenaar, D. A., Gaudry, Q., Karakossian, M. H., Otis, T. S., Kristan, W. B., Trauner, D., & Kramer, R. H. (2008). Photochemical control of endogenous ion channels and cellular excitability. Nature methods, 5(4), 331-338. https://doi.org/10.1038/nmeth.1187