title: Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons.
abstract: Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and can be activated by a number of endogenous inflammatory mediators. A recent study has reported a synergistic effect of simultaneous TRPA1 and TRPV1 activations in vagal pulmonary C-fiber afferents in anesthetized rats, but its underlying mechanism was not known. This study aimed to characterize a possible interaction between these two TRP channels and to investigate the potential role of Ca(2+) as a mediator of this interaction in isolated rat vagal pulmonary sensory neurons. Using the perforated patch-clamp recording technique, our study demonstrated a distinct positive interaction occurring abruptly between TRPA1 and TRPV1 when they were activated simultaneously by their respective agonists, capsaicin (Cap) and allyl isothiocyanate (AITC), at near-threshold concentrations in these neurons. AITC at this low concentration evoked only minimal or undetectable responses, but it markedly amplified the Cap-evoked current in the same neurons. This potentiating effect was eliminated when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, when Ca(2+) was removed from the extracellular solution, the synergistic effect of Cap and AITC on pulmonary sensory neurons was completely abrogated, clearly indicating a critical role of Ca(2+) in mediating the action. These results suggest that this TRPA1-TRPV1 interaction may play a part in regulating the sensitivity of pulmonary sensory neurons during airway inflammatory reaction.
authors: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Chun-Chun
authors: CC
authors: Hsu
authors: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky lylee@uky.edu.
authors: Lu-Yuan
authors: LY
authors: Lee
mesh_terms: D000818:Animals; D001980:Bronchi / Q000294:innervation*; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004357:Drug Synergism; D007477:Ions; D008168:Lung / Q000294:innervation*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D002120:Calcium Channel Agonists; D007477:Ions; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D002211:Capsaicin; D002118:Calcium
keywords: airway; inflammation; sensory nerve; transient receptor potential ankyrin 1; transient receptor potential vanilloid 1