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Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle
Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-indu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japan Society of Smooth Muscle Research
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131261/ https://www.ncbi.nlm.nih.gov/pubmed/24662476 http://dx.doi.org/10.1540/jsmr.49.112 |
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author | Yim, Peter D. Gallos, George Perez-zoghbi, Jose F. Trice, Jacquelyn Zhang, Yi Siviski, Matthew Sonett, Joshua Emala, Charles W. |
author_facet | Yim, Peter D. Gallos, George Perez-zoghbi, Jose F. Trice, Jacquelyn Zhang, Yi Siviski, Matthew Sonett, Joshua Emala, Charles W. |
author_sort | Yim, Peter D. |
collection | PubMed |
description | Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. |
format | Online Article Text |
id | pubmed-4131261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Japan Society of Smooth Muscle Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-41312612014-08-14 Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle Yim, Peter D. Gallos, George Perez-zoghbi, Jose F. Trice, Jacquelyn Zhang, Yi Siviski, Matthew Sonett, Joshua Emala, Charles W. J Smooth Muscle Res Original Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. Japan Society of Smooth Muscle Research 2014-03-21 2013 /pmc/articles/PMC4131261/ /pubmed/24662476 http://dx.doi.org/10.1540/jsmr.49.112 Text en ©2013 The Japan Society of Smooth Muscle Research http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
spellingShingle | Original Yim, Peter D. Gallos, George Perez-zoghbi, Jose F. Trice, Jacquelyn Zhang, Yi Siviski, Matthew Sonett, Joshua Emala, Charles W. Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle |
title | Chloride channel blockers promote relaxation of TEA-induced contraction in
airway smooth muscle |
title_full | Chloride channel blockers promote relaxation of TEA-induced contraction in
airway smooth muscle |
title_fullStr | Chloride channel blockers promote relaxation of TEA-induced contraction in
airway smooth muscle |
title_full_unstemmed | Chloride channel blockers promote relaxation of TEA-induced contraction in
airway smooth muscle |
title_short | Chloride channel blockers promote relaxation of TEA-induced contraction in
airway smooth muscle |
title_sort | chloride channel blockers promote relaxation of tea-induced contraction in
airway smooth muscle |
topic | Original |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131261/ https://www.ncbi.nlm.nih.gov/pubmed/24662476 http://dx.doi.org/10.1540/jsmr.49.112 |
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