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TRPA1 is a major oxidant sensor in murine airway sensory neurons
- Source :
- Journal of Clinical Investigation. May, 2008, Vol. 118 Issue 5, p1899, 12 p.
- Publication Year :
- 2008
-
Abstract
- 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.sup.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.<br />Introduction Chemosensory nerve endings in the airways constantly monitor the chemical composition of the inspired air (1). Airway nerve endings in the nasal passages and bronchi are particularly sensitive to [...]
- Subjects :
- Sensory receptors -- Physiological aspects
Sensory receptors -- Genetic aspects
Sensory receptors -- Research
Airway obstruction (Medicine) -- Risk factors
Airway obstruction (Medicine) -- Genetic aspects
Airway obstruction (Medicine) -- Research
Gene expression -- Health aspects
Gene expression -- Methods
Gene expression -- Research
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 118
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.179043961