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The Journal of Neuroscience, October 17, 2007, 27(42):11412-11415; doi:10.1523/JNEUROSCI.3600-07.2007

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Brief Communications
An Ion Channel Essential for Sensing Chemical Damage

Lindsey J. Macpherson,1 * Bailong Xiao,1 * Kelvin Y. Kwan,2 * Matt J. Petrus,3 Adrienne E. Dubin,1 SunWook Hwang,4 Benjamin Cravatt,1 David P. Corey,2 and Ardem Patapoutian1,3

1Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, 2Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, 3Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, and 4College of Medicine, Korea University, Seoul 136-705, South Korea

Correspondence should be addressed to Dr. Ardem Patapoutian, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 210F, La Jolla, CA 92037. Email: apatapou{at}gnf.org

Tissue damage and its downstream consequences are experimentally assayed by formaldehyde application, which indiscriminately modifies proteins and is presumed to cause pain through broadly acting mechanisms. Here we show that formaldehyde activates the ion channel TRPA1 and that TRPA1-deficient mice exhibit dramatically reduced formaldehyde-induced pain responses. 4-Hydroxynonenal, a reactive chemical produced endogenously during oxidative stress, and other related aldehydes also activate TRPA1 in vitro. Furthermore, painful responses to iodoacetamide, a nonspecific cysteine-alkylating compound, are abolished in TRPA1-deficient mice. Therefore, although these reactive chemicals modify many proteins, the associated pain appears mainly dependent on a single ion channel.

Key words: formaldehyde; TRPA1; TRP; thermoTRP; 4-HNE; pain; somatosensory

Received Aug. 8, 2007; revised Sept. 4, 2007; accepted Sept. 5, 2007.

Correspondence should be addressed to Dr. Ardem Patapoutian, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 210F, La Jolla, CA 92037. Email: apatapou{at}gnf.org


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