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Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle

Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca(2+) channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We...

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Autores principales: Zhang, Ting, Luo, Xiao-Jing, Sai, Wen-Bo, Yu, Meng-Fei, Li, Wen-Er, Ma, Yun-Fei, Chen, Weiwei, Zhai, Kui, Qin, Gangjian, Guo, Donglin, Zheng, Yun-Min, Wang, Yong-Xiao, Shen, Jin-Hua, Ji, Guangju, Liu, Qing-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081631/
https://www.ncbi.nlm.nih.gov/pubmed/24992312
http://dx.doi.org/10.1371/journal.pone.0101578
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author Zhang, Ting
Luo, Xiao-Jing
Sai, Wen-Bo
Yu, Meng-Fei
Li, Wen-Er
Ma, Yun-Fei
Chen, Weiwei
Zhai, Kui
Qin, Gangjian
Guo, Donglin
Zheng, Yun-Min
Wang, Yong-Xiao
Shen, Jin-Hua
Ji, Guangju
Liu, Qing-Hua
author_facet Zhang, Ting
Luo, Xiao-Jing
Sai, Wen-Bo
Yu, Meng-Fei
Li, Wen-Er
Ma, Yun-Fei
Chen, Weiwei
Zhai, Kui
Qin, Gangjian
Guo, Donglin
Zheng, Yun-Min
Wang, Yong-Xiao
Shen, Jin-Hua
Ji, Guangju
Liu, Qing-Hua
author_sort Zhang, Ting
collection PubMed
description Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca(2+) channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca(2+) elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca(2+)-free conditions, and, following a restoration of Ca(2+), a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca(2+) elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.
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spelling pubmed-40816312014-07-10 Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle Zhang, Ting Luo, Xiao-Jing Sai, Wen-Bo Yu, Meng-Fei Li, Wen-Er Ma, Yun-Fei Chen, Weiwei Zhai, Kui Qin, Gangjian Guo, Donglin Zheng, Yun-Min Wang, Yong-Xiao Shen, Jin-Hua Ji, Guangju Liu, Qing-Hua PLoS One Research Article Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca(2+) channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca(2+) elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca(2+)-free conditions, and, following a restoration of Ca(2+), a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca(2+) elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle. Public Library of Science 2014-07-03 /pmc/articles/PMC4081631/ /pubmed/24992312 http://dx.doi.org/10.1371/journal.pone.0101578 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Ting
Luo, Xiao-Jing
Sai, Wen-Bo
Yu, Meng-Fei
Li, Wen-Er
Ma, Yun-Fei
Chen, Weiwei
Zhai, Kui
Qin, Gangjian
Guo, Donglin
Zheng, Yun-Min
Wang, Yong-Xiao
Shen, Jin-Hua
Ji, Guangju
Liu, Qing-Hua
Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title_full Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title_fullStr Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title_full_unstemmed Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title_short Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle
title_sort non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081631/
https://www.ncbi.nlm.nih.gov/pubmed/24992312
http://dx.doi.org/10.1371/journal.pone.0101578
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