2. Academic Validation
  3. Photochemical activation of TRPA1 channels in neurons and animals

Photochemical activation of TRPA1 channels in neurons and animals

  • Nat Chem Biol. 2013 Apr;9(4):257-63. doi: 10.1038/nchembio.1183.
David Kokel 1,  Chung Yan J Cheung,  Robert Mills,  Jaeda Coutinho-Budd,  Liyi Huang,  Vincent Setola,  Jared Sprague,  Shan Jin,  Youngnam N Jin,  Xi-Ping Huang,  Giancarlo Bruni,  Clifford J Woolf,  Bryan L Roth,  Michael R Hamblin,  Mark J Zylka,  David J Milan,  Randall T Peterson
Affiliations

Affiliation

  • 1 Department of Medicine, Cardiovascular Research Center and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA. dkokel@cvrc.mgh.harvard.edu
PMID: 23396078 DOI: 10.1038/nchembio.1183
Abstract

Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and Other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild-type zebrafish and mice. To our surprise, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In Animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in nontransgenic Animals, including humans.

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