Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels

Thomas E. Taylor-Clark, Bradley J Undem

Research output: Contribution to journalArticle

Abstract

Inhalation of ozone is a major health risk in industrialized nations. Ozone can impair lung function and induce respiratory symptoms through sensory neural-mediated pathways, yet the specific interaction of ozone with airway sensory nerves has yet to be elucidated. Here we demonstrate, using a vagally innervated ex vivo tracheal-lung mouse preparation, that ozone selectively and directly evokes action potential discharge in a subset of nociceptive bronchopulmonary nerves, namely slow conducting C-fibres. Sensitivity to ozone correlated with the transient receptor potential (TRP) A1 agonist, cinnamaldehyde, with ozone having no effect on cinnamaldehyde-insensitive fibres. C-fibre responses to ozone were abolished by ruthenium red (TRP inhibitor). Ozone also stimulated a subset of nociceptive sensory neurones isolated from vagal ganglia of wild-type mice, but failed to activate neurones isolated from transient receptor potential ankyrin 1 (TRPA1) knockout mice. Ozone activated HEK293 cells transfected with TRPA1, but failed to activate non-transfected HEK293 or HEK293 transfected with the capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1) channel. Thus, ozone is not an indiscriminate neuronal activator, but rather it potently and selectively activates a subset of airway C-fibres by directly stimulating TRPA1.

Original languageEnglish (US)
Pages (from-to)423-433
Number of pages11
JournalJournal of Physiology
Volume588
Issue number3
DOIs
StatePublished - Feb 2010

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Ankyrins
Ozone
Ion Channels
Unmyelinated Nerve Fibers
Ruthenium Red
Neural Pathways
Lung
Nociceptors
HEK293 Cells
Capsaicin
Sensory Receptor Cells
Developed Countries
Knockout Mice
Ganglia
Inhalation
Action Potentials

ASJC Scopus subject areas

  • Physiology

Cite this

Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels. / Taylor-Clark, Thomas E.; Undem, Bradley J.

In: Journal of Physiology, Vol. 588, No. 3, 02.2010, p. 423-433.

Research output: Contribution to journalArticle

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