Imperial College London
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DrMarkBirrell

Faculty of Medicine, National Heart & Lung Institute

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 8578m.birrell

 
 
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Location

 

103Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Belvisi:2016:10.1016/j.jaci.2015.10.044,
author = {Belvisi, MG},
doi = {10.1016/j.jaci.2015.10.044},
journal = {Journal of Allergy and Clinical Immunology},
pages = {249--261.e12},
title = {Transient receptor potential cation channel, subfamily V, member 4 and airway, sensory afferent activation: role of adenosine triphosphate},
url = {http://dx.doi.org/10.1016/j.jaci.2015.10.044},
volume = {138},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.
AU  - Belvisi,MG
DO  - 10.1016/j.jaci.2015.10.044
EP  - 261
PY  - 2016///
SN  - 1097-6825
SP  - 249
TI  - Transient receptor potential cation channel, subfamily V, member 4 and airway, sensory afferent activation: role of adenosine triphosphate
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2015.10.044
UR  - http://hdl.handle.net/10044/1/28232
VL  - 138
ER  -
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