Serveur d'exploration Chloroquine

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Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.

Identifieur interne : 000E80 ( Main/Exploration ); précédent : 000E79; suivant : 000E81

Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.

Auteurs : Ming-Yu Wei [République populaire de Chine] ; Lu Xue [République populaire de Chine] ; Li Tan [République populaire de Chine] ; Wen-Bo Sai [République populaire de Chine] ; Xiao-Cao Liu [République populaire de Chine] ; Qiu-Ju Jiang [République populaire de Chine] ; Jinhua Shen [République populaire de Chine] ; Yong-Bo Peng [République populaire de Chine] ; Ping Zhao [République populaire de Chine] ; Meng-Fei Yu [République populaire de Chine] ; Weiwei Chen [République populaire de Chine] ; Li-Qun Ma [République populaire de Chine] ; Kui Zhai [République populaire de Chine] ; Chunbin Zou [États-Unis] ; Donglin Guo [États-Unis] ; Gangjian Qin [États-Unis] ; Yun-Min Zheng [États-Unis] ; Yong-Xiao Wang [États-Unis] ; Guangju Ji [République populaire de Chine] ; Qing-Hua Liu [République populaire de Chine]

Source :

RBID : pubmed:25822280

Descripteurs français

English descriptors

Abstract

The participation of large-conductance Ca2+ 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 Ca2+ sparks and caffeine-induced global Ca2+ 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.

DOI: 10.1371/journal.pone.0121566
PubMed: 25822280


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<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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<name sortKey="Zhai, Kui" sort="Zhai, Kui" uniqKey="Zhai K" first="Kui" last="Zhai">Kui Zhai</name>
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<nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
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<settlement type="city">Pékin</settlement>
</placeName>
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<nlm:affiliation>Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213</wicri:regionArea>
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<settlement type="city">Pittsburgh</settlement>
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<name sortKey="Guo, Donglin" sort="Guo, Donglin" uniqKey="Guo D" first="Donglin" last="Guo">Donglin Guo</name>
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<nlm:affiliation>Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096, United States of America.</nlm:affiliation>
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<wicri:regionArea>Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096</wicri:regionArea>
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<wicri:regionArea>Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611</wicri:regionArea>
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<region type="state">Illinois</region>
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<name sortKey="Wang, Yong Xiao" sort="Wang, Yong Xiao" uniqKey="Wang Y" first="Yong-Xiao" last="Wang">Yong-Xiao Wang</name>
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<nlm:affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208</wicri:regionArea>
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<region type="state">État de New York</region>
</placeName>
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<author>
<name sortKey="Ji, Guangju" sort="Ji, Guangju" uniqKey="Ji G" first="Guangju" last="Ji">Guangju Ji</name>
<affiliation wicri:level="1">
<nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
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<settlement type="city">Pékin</settlement>
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</author>
<author>
<name sortKey="Liu, Qing Hua" sort="Liu, Qing Hua" uniqKey="Liu Q" first="Qing-Hua" last="Liu">Qing-Hua Liu</name>
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<nlm:affiliation>Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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<series>
<title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
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<date when="2015" type="published">2015</date>
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<term>Animals</term>
<term>Calcium Channel Blockers (pharmacology)</term>
<term>Calcium Signaling (drug effects)</term>
<term>Chloroquine (pharmacology)</term>
<term>In Vitro Techniques</term>
<term>Large-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors)</term>
<term>Large-Conductance Calcium-Activated Potassium Channels (physiology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Muscle Contraction (drug effects)</term>
<term>Muscle Contraction (physiology)</term>
<term>Muscle, Smooth (drug effects)</term>
<term>Muscle, Smooth (physiology)</term>
<term>Myocytes, Smooth Muscle (drug effects)</term>
<term>Myocytes, Smooth Muscle (physiology)</term>
<term>Patch-Clamp Techniques</term>
<term>Peptides (pharmacology)</term>
<term>Ryanodine Receptor Calcium Release Channel (physiology)</term>
<term>Trachea (cytology)</term>
<term>Trachea (physiology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Canal de libération du calcium du récepteur à la ryanodine (physiologie)</term>
<term>Canaux potassiques calcium-dépendants de grande conductance (antagonistes et inhibiteurs)</term>
<term>Canaux potassiques calcium-dépendants de grande conductance (physiologie)</term>
<term>Chloroquine (pharmacologie)</term>
<term>Contraction musculaire ()</term>
<term>Contraction musculaire (physiologie)</term>
<term>Inhibiteurs des canaux calciques (pharmacologie)</term>
<term>Muscles lisses ()</term>
<term>Muscles lisses (physiologie)</term>
<term>Myocytes du muscle lisse ()</term>
<term>Myocytes du muscle lisse (physiologie)</term>
<term>Mâle</term>
<term>Peptides (pharmacologie)</term>
<term>Signalisation du calcium ()</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Techniques de patch-clamp</term>
<term>Techniques in vitro</term>
<term>Trachée (cytologie)</term>
<term>Trachée (physiologie)</term>
</keywords>
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<term>Large-Conductance Calcium-Activated Potassium Channels</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Calcium Channel Blockers</term>
<term>Chloroquine</term>
<term>Peptides</term>
</keywords>
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<term>Canaux potassiques calcium-dépendants de grande conductance</term>
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<term>Trachée</term>
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<term>Trachea</term>
</keywords>
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<term>Calcium Signaling</term>
<term>Muscle Contraction</term>
<term>Muscle, Smooth</term>
<term>Myocytes, Smooth Muscle</term>
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<term>Chloroquine</term>
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<term>Myocytes du muscle lisse</term>
<term>Trachée</term>
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<term>Large-Conductance Calcium-Activated Potassium Channels</term>
<term>Muscle Contraction</term>
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<term>Animals</term>
<term>In Vitro Techniques</term>
<term>Male</term>
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<term>Patch-Clamp Techniques</term>
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<term>Animaux</term>
<term>Contraction musculaire</term>
<term>Muscles lisses</term>
<term>Myocytes du muscle lisse</term>
<term>Mâle</term>
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<term>Souris</term>
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<front>
<div type="abstract" xml:lang="en">The participation of large-conductance Ca2+ 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 Ca2+ sparks and caffeine-induced global Ca2+ 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. </div>
</front>
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<li>États-Unis</li>
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<li>Pennsylvanie</li>
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<name sortKey="Liu, Xiao Cao" sort="Liu, Xiao Cao" uniqKey="Liu X" first="Xiao-Cao" last="Liu">Xiao-Cao Liu</name>
<name sortKey="Ma, Li Qun" sort="Ma, Li Qun" uniqKey="Ma L" first="Li-Qun" last="Ma">Li-Qun Ma</name>
<name sortKey="Peng, Yong Bo" sort="Peng, Yong Bo" uniqKey="Peng Y" first="Yong-Bo" last="Peng">Yong-Bo Peng</name>
<name sortKey="Sai, Wen Bo" sort="Sai, Wen Bo" uniqKey="Sai W" first="Wen-Bo" last="Sai">Wen-Bo Sai</name>
<name sortKey="Shen, Jinhua" sort="Shen, Jinhua" uniqKey="Shen J" first="Jinhua" last="Shen">Jinhua Shen</name>
<name sortKey="Tan, Li" sort="Tan, Li" uniqKey="Tan L" first="Li" last="Tan">Li Tan</name>
<name sortKey="Xue, Lu" sort="Xue, Lu" uniqKey="Xue L" first="Lu" last="Xue">Lu Xue</name>
<name sortKey="Yu, Meng Fei" sort="Yu, Meng Fei" uniqKey="Yu M" first="Meng-Fei" last="Yu">Meng-Fei Yu</name>
<name sortKey="Zhai, Kui" sort="Zhai, Kui" uniqKey="Zhai K" first="Kui" last="Zhai">Kui Zhai</name>
<name sortKey="Zhao, Ping" sort="Zhao, Ping" uniqKey="Zhao P" first="Ping" last="Zhao">Ping Zhao</name>
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<name sortKey="Zou, Chunbin" sort="Zou, Chunbin" uniqKey="Zou C" first="Chunbin" last="Zou">Chunbin Zou</name>
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