Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons

Chun-Chun Hsu, Lu-Yuan Lee

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 Ca2+ 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 Ca2+ 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 Ca2+ 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. Copyright © 2015 the American Physiological Society.
Original languageEnglish
Pages (from-to)1533-1543
Number of pages11
JournalJournal of Applied Physiology
Volume118
Issue number12
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Ankyrins
Sensory Receptor Cells
Capsaicin
Ions
Calcium
Lung
Unmyelinated Nerve Fibers
Neurons
Patch-Clamp Techniques
allyl isothiocyanate

Keywords

  • Airway
  • Inflammation
  • Sensory nerve
  • Transient receptor potential ankyrin 1
  • Transient receptor potential vanilloid 1

Cite this

Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons. / Hsu, Chun-Chun; Lee, Lu-Yuan.

In: Journal of Applied Physiology, Vol. 118, No. 12, 2015, p. 1533-1543.

Research output: Contribution to journalArticle

@article{28ef9f6e15be4298824b246ba955ed12,
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 Ca2+ 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 Ca2+ 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 Ca2+ 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. Copyright {\circledC} 2015 the American Physiological Society.",
keywords = "Airway, Inflammation, Sensory nerve, Transient receptor potential ankyrin 1, Transient receptor potential vanilloid 1",
author = "Chun-Chun Hsu and Lu-Yuan Lee",
note = "被引用次數:1 Export Date: 11 May 2016 CODEN: JAPHE 通訊地址: Lee, L.-Y.; Department of Physiology, University of Kentucky Medical CenterUnited States 出資詳情: HL-96914, NIH, National Institutes of Health 出資詳情: UL1TR0000117, NIH, National Institutes of Health 參考文獻: Ahern, G.P., Brooks, I.M., Miyares, R.L., Wang, X.B., Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling (2005) J Neurosci, 25, pp. 5109-5116; Akopian, A.N., Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions (2011) Curr Pharm Biotechnol, 12, pp. 89-94; Bandell, M., Story, G.M., Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J., Patapoutian, A., Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin (2004) Neuron, 41, pp. 849-857; Bautista, D.M., Jordt, S.E., Nikai, T., Tsuruda, P.R., Read, A.J., Poblete, J., Yamoah, E.N., Julius, D., TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents (2006) Cell, 124, pp. 1269-1282; Bautista, D.M., Pellegrino, M., Tsunozaki, M., TRPA1: A gatekeeper for inflammation (2013) Annu Rev Physiol, 75, pp. 181-200; Caceres, A.I., Brackmann, M., Elia, M.D., Bessac, B.F., Del Camino, D., D'Amours, M., Witek, J.S., Jordt, S.E., A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma (2009) Proc Natl Acad Sci USA, 106, pp. 9099-9104; Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., Julius, D., The capsaicin receptor: A heat-activated ion channel in the pain pathway (1997) Nature, 389, pp. 816-824; Cavanaugh, E.J., Simkin, D., Kim, D., Activation of transient receptor potential A1 channels by mustard oil, tetrahydrocannabinol and Ca2+ reveals different functional channel states (2008) Neuroscience, 154, pp. 1467-1476; Coleridge, J.C., Coleridge, H.M., Afferent vagal C fibre innervation of the lungs and airways and its functional significance (1984) Rev Physiol Biochem Pharmacol, 99, pp. 1-110; Doerner, J.F., Gisselmann, G., Hatt, H., Wetzel, C.H., Transient receptor potential channel A1 is directly gated by calcium ions (2007) J Biol Chem, 282, pp. 13180-13189; Fernandes, E.S., Fernandes, M.A., Keeble, J.E., The functions of TRPA1 and TRPV1: Moving away from sensory nerves (2012) Br J Pharmacol, 166, pp. 510-521; Gees, M., Owsianik, G., Nilius, B., Voets, T., TRP channels (2012) Compr Physiol, 2, pp. 563-608; Geppetti, P., Materazzi, S., Nicoletti, P., The transient receptor potential vanilloid 1: Role in airway inflammation and disease (2006) Eur J Pharmacol, 533, pp. 207-214; Gu, Q., Kwong, K., Lee, L.Y., Ca2+ transient evoked by chemical stimulation is enhanced by PGE<inf>2</inf> in vagal sensory neurons: Role of cAMP/PKA signaling pathway (2003) J Neurophysiol, 89, pp. 1985-1993; Gu, Q., Lee, L.Y., Characterization of acid signaling in rat vagal pulmonary sensory neurons (2006) Am J Physiol Lung Cell Mol Physiol, 291, pp. L58-L65; Hellwig, N., Albrecht, N., Harteneck, C., Schultz, G., Schaefer, M., Homoand heteromeric assembly of TRPV channel subunits (2005) J Cell Sci, 118, pp. 917-928; Jammes, Y., Fornaris, E., Mei, N., Barrat, E., Afferent and efferent components of the bronchial vagal branches in cats (1982) J Auton Nerv Syst, 5, pp. 165-176; Kwong, K., Kollarik, M., Nassenstein, C., Ru, F., Undem, B.J., P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus (2008) Am J Physiol Lung Cell Mol Physiol, 295, pp. L858-L865; Kwong, K., Lee, L.Y., PGE(2) sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli (2002) J Appl Physiol, 93, pp. 1419-1428; Lee, L.Y., Gu, Q., Role of TRPV1 in inflammation-induced airway hypersensitivity (2009) Curr Opin Pharmacol, 9, pp. 243-249; Lee, L.Y., Yu, J., Sensory nerves in lung and airways (2014) Compr Physiol, 4, pp. 287-324; Lin, Y.J., Lin, R.L., Ruan, T., Khosravi, M., Lee, L.Y., A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents (2015) J Appl Physiol, 118, pp. 273-281; McMahon, S.B., Wood, J.N., Increasingly irritable and close to tears: TRPA1 in inflammatory pain (2006) Cell, 124, pp. 1123-1125; Miyamoto, T., Dubin, A.E., Petrus, M.J., Patapoutian, A., TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice (2009) PLoS One, 4; Nassenstein, C., Kwong, K., Taylor-Clark, T., Kollarik, M., Macglashan, D.M., Braun, A., Undem, B.J., Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs (2008) J Physiol, 586, pp. 1595-1604; Nassini, R., Pedretti, P., Moretto, N., Fusi, C., Carnini, C., Facchinetti, F., Viscomi, A.R., Materazzi, S., Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation (2012) PLoS One, 7; Ni, D., Lee, L.Y., Effect of increasing temperature on TRPV1-mediated responses in isolated rat pulmonary sensory neurons (2008) Am J Physiol Lung Cell Mol Physiol, 294, pp. L563-L571; Nilius, B., Appendino, G., Owsianik, G., The transient receptor potential channel TRPA1: From gene to pathophysiology (2012) Pfl{\"u}gers Arch, 464, pp. 425-458; Nilius, B., Owsianik, G., Voets, T., Peters, J.A., Transient receptor potential cation channels in disease (2007) Physiol Rev, 87, pp. 165-217; Park, J.Y., Hwang, E.M., Yarishkin, O., Seo, J.H., Kim, E., Yoo, J., Yi, G.S., Hong, S.G., TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel (2008) Biochem Biophys Res Commun, 368, pp. 677-683; Patil, M.J., Jeske, N.A., Akopian, A.N., Transient receptor potential V1 regulates activation and modulation of transient receptor potential A1 by Ca2+ (2010) Neuroscience, 171, pp. 1109-1119; Ruparel, N.B., Patwardhan, A.M., Akopian, A.N., Hargreaves, K.M., Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine (2011) Mol Pharmacol, 80, pp. 117-123; Salas, M.M., Hargreaves, K.M., Akopian, A.N., TRPA1-mediated responses in trigeminal sensory neurons: Interaction between TRPA1 and TRPV1 (2009) Eur J Neurosci, 29, pp. 1568-1578; Spahn, V., Stein, C., Zollner, C., Modulation of transient receptor vanilloid 1 activity by transient receptor potential ankyrin 1 (2014) Mol Pharmacol, 85, pp. 335-344; Staruschenko, A., Jeske, N.A., Akopian, A.N., Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel (2010) J Biol Chem, 285, pp. 15167-15177; Story, G.M., Peier, A.M., Reeve, A.J., Eid, S.R., Mosbacher, J., Hricik, T.R., Earley, T.J., Patapoutian, A., ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures (2003) Cell, 112, pp. 819-829; Taylor-Clark, T.E., McAlexander, M.A., Nassenstein, C., Sheardown, S.A., Wilson, S., Thornton, J., Carr, M.J., Undem, B.J., Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal (2008) J Physiol, 586, pp. 3447-3459; Wang, Y.Y., Chang, R.B., Waters, H.N., McKemy, D.D., Liman, E.R., The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions (2008) J Biol Chem, 283, pp. 32691-32703; Weng, H.J., Patel, K.N., Jeske, N.A., Bierbower, S.M., Zou, W., Tiwari, V., Zheng, Q., Dong, X., Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain (2015) Neuron, 85, pp. 833-846; Zurborg, S., Yurgionas, B., Jira, J.A., Caspani, O., Heppenstall, P.A., Direct activation of the ion channel TRPA1 by Ca2+ (2007) Nat Neurosci, 10, pp. 277-279",
year = "2015",
doi = "10.1152/japplphysiol.00043.2015",
language = "English",
volume = "118",
pages = "1533--1543",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "12",

}

TY - JOUR

T1 - Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons

AU - Hsu, Chun-Chun

AU - Lee, Lu-Yuan

N1 - 被引用次數:1 Export Date: 11 May 2016 CODEN: JAPHE 通訊地址: Lee, L.-Y.; Department of Physiology, University of Kentucky Medical CenterUnited States 出資詳情: HL-96914, NIH, National Institutes of Health 出資詳情: UL1TR0000117, NIH, National Institutes of Health 參考文獻: Ahern, G.P., Brooks, I.M., Miyares, R.L., Wang, X.B., Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling (2005) J Neurosci, 25, pp. 5109-5116; Akopian, A.N., Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions (2011) Curr Pharm Biotechnol, 12, pp. 89-94; Bandell, M., Story, G.M., Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J., Patapoutian, A., Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin (2004) Neuron, 41, pp. 849-857; Bautista, D.M., Jordt, S.E., Nikai, T., Tsuruda, P.R., Read, A.J., Poblete, J., Yamoah, E.N., Julius, D., TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents (2006) Cell, 124, pp. 1269-1282; Bautista, D.M., Pellegrino, M., Tsunozaki, M., TRPA1: A gatekeeper for inflammation (2013) Annu Rev Physiol, 75, pp. 181-200; Caceres, A.I., Brackmann, M., Elia, M.D., Bessac, B.F., Del Camino, D., D'Amours, M., Witek, J.S., Jordt, S.E., A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma (2009) Proc Natl Acad Sci USA, 106, pp. 9099-9104; Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., Julius, D., The capsaicin receptor: A heat-activated ion channel in the pain pathway (1997) Nature, 389, pp. 816-824; Cavanaugh, E.J., Simkin, D., Kim, D., Activation of transient receptor potential A1 channels by mustard oil, tetrahydrocannabinol and Ca2+ reveals different functional channel states (2008) Neuroscience, 154, pp. 1467-1476; Coleridge, J.C., Coleridge, H.M., Afferent vagal C fibre innervation of the lungs and airways and its functional significance (1984) Rev Physiol Biochem Pharmacol, 99, pp. 1-110; Doerner, J.F., Gisselmann, G., Hatt, H., Wetzel, C.H., Transient receptor potential channel A1 is directly gated by calcium ions (2007) J Biol Chem, 282, pp. 13180-13189; Fernandes, E.S., Fernandes, M.A., Keeble, J.E., The functions of TRPA1 and TRPV1: Moving away from sensory nerves (2012) Br J Pharmacol, 166, pp. 510-521; Gees, M., Owsianik, G., Nilius, B., Voets, T., TRP channels (2012) Compr Physiol, 2, pp. 563-608; Geppetti, P., Materazzi, S., Nicoletti, P., The transient receptor potential vanilloid 1: Role in airway inflammation and disease (2006) Eur J Pharmacol, 533, pp. 207-214; Gu, Q., Kwong, K., Lee, L.Y., Ca2+ transient evoked by chemical stimulation is enhanced by PGE<inf>2</inf> in vagal sensory neurons: Role of cAMP/PKA signaling pathway (2003) J Neurophysiol, 89, pp. 1985-1993; Gu, Q., Lee, L.Y., Characterization of acid signaling in rat vagal pulmonary sensory neurons (2006) Am J Physiol Lung Cell Mol Physiol, 291, pp. L58-L65; Hellwig, N., Albrecht, N., Harteneck, C., Schultz, G., Schaefer, M., Homoand heteromeric assembly of TRPV channel subunits (2005) J Cell Sci, 118, pp. 917-928; Jammes, Y., Fornaris, E., Mei, N., Barrat, E., Afferent and efferent components of the bronchial vagal branches in cats (1982) J Auton Nerv Syst, 5, pp. 165-176; Kwong, K., Kollarik, M., Nassenstein, C., Ru, F., Undem, B.J., P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus (2008) Am J Physiol Lung Cell Mol Physiol, 295, pp. L858-L865; Kwong, K., Lee, L.Y., PGE(2) sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli (2002) J Appl Physiol, 93, pp. 1419-1428; Lee, L.Y., Gu, Q., Role of TRPV1 in inflammation-induced airway hypersensitivity (2009) Curr Opin Pharmacol, 9, pp. 243-249; Lee, L.Y., Yu, J., Sensory nerves in lung and airways (2014) Compr Physiol, 4, pp. 287-324; Lin, Y.J., Lin, R.L., Ruan, T., Khosravi, M., Lee, L.Y., A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents (2015) J Appl Physiol, 118, pp. 273-281; McMahon, S.B., Wood, J.N., Increasingly irritable and close to tears: TRPA1 in inflammatory pain (2006) Cell, 124, pp. 1123-1125; Miyamoto, T., Dubin, A.E., Petrus, M.J., Patapoutian, A., TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice (2009) PLoS One, 4; Nassenstein, C., Kwong, K., Taylor-Clark, T., Kollarik, M., Macglashan, D.M., Braun, A., Undem, B.J., Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs (2008) J Physiol, 586, pp. 1595-1604; Nassini, R., Pedretti, P., Moretto, N., Fusi, C., Carnini, C., Facchinetti, F., Viscomi, A.R., Materazzi, S., Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation (2012) PLoS One, 7; Ni, D., Lee, L.Y., Effect of increasing temperature on TRPV1-mediated responses in isolated rat pulmonary sensory neurons (2008) Am J Physiol Lung Cell Mol Physiol, 294, pp. L563-L571; Nilius, B., Appendino, G., Owsianik, G., The transient receptor potential channel TRPA1: From gene to pathophysiology (2012) Pflügers Arch, 464, pp. 425-458; Nilius, B., Owsianik, G., Voets, T., Peters, J.A., Transient receptor potential cation channels in disease (2007) Physiol Rev, 87, pp. 165-217; Park, J.Y., Hwang, E.M., Yarishkin, O., Seo, J.H., Kim, E., Yoo, J., Yi, G.S., Hong, S.G., TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel (2008) Biochem Biophys Res Commun, 368, pp. 677-683; Patil, M.J., Jeske, N.A., Akopian, A.N., Transient receptor potential V1 regulates activation and modulation of transient receptor potential A1 by Ca2+ (2010) Neuroscience, 171, pp. 1109-1119; Ruparel, N.B., Patwardhan, A.M., Akopian, A.N., Hargreaves, K.M., Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine (2011) Mol Pharmacol, 80, pp. 117-123; Salas, M.M., Hargreaves, K.M., Akopian, A.N., TRPA1-mediated responses in trigeminal sensory neurons: Interaction between TRPA1 and TRPV1 (2009) Eur J Neurosci, 29, pp. 1568-1578; Spahn, V., Stein, C., Zollner, C., Modulation of transient receptor vanilloid 1 activity by transient receptor potential ankyrin 1 (2014) Mol Pharmacol, 85, pp. 335-344; Staruschenko, A., Jeske, N.A., Akopian, A.N., Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel (2010) J Biol Chem, 285, pp. 15167-15177; Story, G.M., Peier, A.M., Reeve, A.J., Eid, S.R., Mosbacher, J., Hricik, T.R., Earley, T.J., Patapoutian, A., ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures (2003) Cell, 112, pp. 819-829; Taylor-Clark, T.E., McAlexander, M.A., Nassenstein, C., Sheardown, S.A., Wilson, S., Thornton, J., Carr, M.J., Undem, B.J., Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal (2008) J Physiol, 586, pp. 3447-3459; Wang, Y.Y., Chang, R.B., Waters, H.N., McKemy, D.D., Liman, E.R., The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions (2008) J Biol Chem, 283, pp. 32691-32703; Weng, H.J., Patel, K.N., Jeske, N.A., Bierbower, S.M., Zou, W., Tiwari, V., Zheng, Q., Dong, X., Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain (2015) Neuron, 85, pp. 833-846; Zurborg, S., Yurgionas, B., Jira, J.A., Caspani, O., Heppenstall, P.A., Direct activation of the ion channel TRPA1 by Ca2+ (2007) Nat Neurosci, 10, pp. 277-279

PY - 2015

Y1 - 2015

N2 - 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 Ca2+ 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 Ca2+ 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 Ca2+ 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. Copyright © 2015 the American Physiological Society.

AB - 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 Ca2+ 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 Ca2+ 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 Ca2+ 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. Copyright © 2015 the American Physiological Society.

KW - Airway

KW - Inflammation

KW - Sensory nerve

KW - Transient receptor potential ankyrin 1

KW - Transient receptor potential vanilloid 1

U2 - 10.1152/japplphysiol.00043.2015

DO - 10.1152/japplphysiol.00043.2015

M3 - Article

VL - 118

SP - 1533

EP - 1543

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 12

ER -