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TRPA1 is a major oxidant sensor in murine airway sensory neurons.

Publication ,  Journal Article
Bessac, BF; Sivula, M; von Hehn, CA; Escalera, J; Cohn, L; Jordt, S-E
Published in: J Clin Invest
May 2008

Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca(2+) influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1(-/-) mice displayed profound deficiencies in hypochlorite- and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 2008

Volume

118

Issue

5

Start / End Page

1899 / 1910

Location

United States

Related Subject Headings

  • Transient Receptor Potential Channels
  • TRPA1 Cation Channel
  • Sodium Hypochlorite
  • Respiratory System
  • Plant Oils
  • Patch-Clamp Techniques
  • Pain
  • Oxidants
  • Neurons, Afferent
  • Mustard Plant
 

Citation

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Bessac, B. F., Sivula, M., von Hehn, C. A., Escalera, J., Cohn, L., & Jordt, S.-E. (2008). TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest, 118(5), 1899–1910. https://doi.org/10.1172/JCI34192
Bessac, Bret F., Michael Sivula, Christian A. von Hehn, Jasmine Escalera, Lauren Cohn, and Sven-Eric Jordt. “TRPA1 is a major oxidant sensor in murine airway sensory neurons.J Clin Invest 118, no. 5 (May 2008): 1899–1910. https://doi.org/10.1172/JCI34192.
Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt S-E. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008 May;118(5):1899–910.
Bessac, Bret F., et al. “TRPA1 is a major oxidant sensor in murine airway sensory neurons.J Clin Invest, vol. 118, no. 5, May 2008, pp. 1899–910. Pubmed, doi:10.1172/JCI34192.
Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt S-E. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008 May;118(5):1899–1910.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 2008

Volume

118

Issue

5

Start / End Page

1899 / 1910

Location

United States

Related Subject Headings

  • Transient Receptor Potential Channels
  • TRPA1 Cation Channel
  • Sodium Hypochlorite
  • Respiratory System
  • Plant Oils
  • Patch-Clamp Techniques
  • Pain
  • Oxidants
  • Neurons, Afferent
  • Mustard Plant