Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels.
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.
Taylor-Clark
Thomas E
TE
Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD, USA. ttaylorc@health.usf.edu
Undem
Bradley J
BJ
D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010126:Ozone / Q000494:pharmacology*; D012137:Respiratory System / Q000294:innervation*; D012430:Ruthenium Red / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D012430:Ruthenium Red; D010126:Ozone; D000171:Acrolein; C012843:cinnamaldehyde