Photochemical control of endogenous ion channels and cellular excitability

Nat Methods. 2008 Apr;5(4):331-8. doi: 10.1038/nmeth.1187. Epub 2008 Mar 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / radiation effects*
  • Affinity Labels / chemistry
  • Animals
  • Azo Compounds / chemistry
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cerebellum / radiation effects
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / radiation effects
  • Ion Channel Gating / radiation effects*
  • Leeches
  • Neurons* / metabolism
  • Neurons* / radiation effects
  • Photic Stimulation
  • Photochemistry
  • Potassium Channels / metabolism*
  • Quaternary Ammonium Compounds / chemistry
  • Rats


  • Affinity Labels
  • Azo Compounds
  • Potassium Channels
  • Quaternary Ammonium Compounds
  • azobenzene