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Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle
The participation of large-conductance Ca(2+) activated K(+) channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked s...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378962/ https://www.ncbi.nlm.nih.gov/pubmed/25822280 http://dx.doi.org/10.1371/journal.pone.0121566 |
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author | Wei, Ming-Yu Xue, Lu Tan, Li Sai, Wen-Bo Liu, Xiao-Cao Jiang, Qiu-Ju Shen, Jinhua Peng, Yong-Bo Zhao, Ping Yu, Meng-Fei Chen, Weiwei Ma, Li-Qun Zhai, Kui Zou, Chunbin Guo, Donglin Qin, Gangjian Zheng, Yun-Min Wang, Yong-Xiao Ji, Guangju Liu, Qing-Hua |
author_facet | Wei, Ming-Yu Xue, Lu Tan, Li Sai, Wen-Bo Liu, Xiao-Cao Jiang, Qiu-Ju Shen, Jinhua Peng, Yong-Bo Zhao, Ping Yu, Meng-Fei Chen, Weiwei Ma, Li-Qun Zhai, Kui Zou, Chunbin Guo, Donglin Qin, Gangjian Zheng, Yun-Min Wang, Yong-Xiao Ji, Guangju Liu, Qing-Hua |
author_sort | Wei, Ming-Yu |
collection | PubMed |
description | The participation of large-conductance Ca(2+) activated K(+) channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked spontaneous transient outward currents (STOCs) in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca(2+) sparks and caffeine-induced global Ca(2+) increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs). We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH). Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax), BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro. |
format | Online Article Text |
id | pubmed-4378962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43789622015-04-09 Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle Wei, Ming-Yu Xue, Lu Tan, Li Sai, Wen-Bo Liu, Xiao-Cao Jiang, Qiu-Ju Shen, Jinhua Peng, Yong-Bo Zhao, Ping Yu, Meng-Fei Chen, Weiwei Ma, Li-Qun Zhai, Kui Zou, Chunbin Guo, Donglin Qin, Gangjian Zheng, Yun-Min Wang, Yong-Xiao Ji, Guangju Liu, Qing-Hua PLoS One Research Article The participation of large-conductance Ca(2+) activated K(+) channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked spontaneous transient outward currents (STOCs) in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca(2+) sparks and caffeine-induced global Ca(2+) increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs). We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH). Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax), BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro. Public Library of Science 2015-03-30 /pmc/articles/PMC4378962/ /pubmed/25822280 http://dx.doi.org/10.1371/journal.pone.0121566 Text en © 2015 Wei 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 Wei, Ming-Yu Xue, Lu Tan, Li Sai, Wen-Bo Liu, Xiao-Cao Jiang, Qiu-Ju Shen, Jinhua Peng, Yong-Bo Zhao, Ping Yu, Meng-Fei Chen, Weiwei Ma, Li-Qun Zhai, Kui Zou, Chunbin Guo, Donglin Qin, Gangjian Zheng, Yun-Min Wang, Yong-Xiao Ji, Guangju Liu, Qing-Hua Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title | Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title_full | Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title_fullStr | Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title_full_unstemmed | Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title_short | Involvement of Large-Conductance Ca(2+)-Activated K(+) Channels in Chloroquine-Induced Force Alterations in Pre-Contracted Airway Smooth Muscle |
title_sort | involvement of large-conductance ca(2+)-activated k(+) channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378962/ https://www.ncbi.nlm.nih.gov/pubmed/25822280 http://dx.doi.org/10.1371/journal.pone.0121566 |
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