Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.
Identifieur interne : 000261 ( PubMed/Corpus ); précédent : 000260; suivant : 000262Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.
Auteurs : Ming-Yu Wei ; Lu Xue ; Li Tan ; Wen-Bo Sai ; Xiao-Cao Liu ; Qiu-Ju Jiang ; Jinhua Shen ; Yong-Bo Peng ; Ping Zhao ; Meng-Fei Yu ; Weiwei Chen ; Li-Qun Ma ; Kui Zhai ; Chunbin Zou ; Donglin Guo ; Gangjian Qin ; Yun-Min Zheng ; Yong-Xiao Wang ; Guangju Ji ; Qing-Hua LiuSource :
- PloS one [ 1932-6203 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Calcium Channel Blockers (pharmacology), Calcium Signaling (drug effects), Chloroquine (pharmacology), In Vitro Techniques, Large-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors), Large-Conductance Calcium-Activated Potassium Channels (physiology), Male, Mice, Mice, Inbred BALB C, Muscle Contraction (drug effects), Muscle Contraction (physiology), Muscle, Smooth (drug effects), Muscle, Smooth (physiology), Myocytes, Smooth Muscle (drug effects), Myocytes, Smooth Muscle (physiology), Patch-Clamp Techniques, Peptides (pharmacology), Ryanodine Receptor Calcium Release Channel (physiology), Trachea (cytology), Trachea (physiology).
- MESH :
- chemical , antagonists & inhibitors : Large-Conductance Calcium-Activated Potassium Channels.
- chemical , pharmacology : Calcium Channel Blockers, Chloroquine, Peptides.
- cytology : Trachea.
- drug effects : Calcium Signaling, Muscle Contraction, Muscle, Smooth, Myocytes, Smooth Muscle.
- chemical , physiology : Large-Conductance Calcium-Activated Potassium Channels, Muscle Contraction, Muscle, Smooth, Myocytes, Smooth Muscle, Ryanodine Receptor Calcium Release Channel, Trachea.
- Animals, In Vitro Techniques, Male, Mice, Mice, Inbred BALB C, Patch-Clamp Techniques.
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
Links to Exploration step
pubmed:25822280Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.</title><author><name sortKey="Wei, Ming Yu" sort="Wei, Ming Yu" uniqKey="Wei M" first="Ming-Yu" last="Wei">Ming-Yu Wei</name><affiliation><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></affiliation></author><author><name sortKey="Xue, Lu" sort="Xue, Lu" uniqKey="Xue L" first="Lu" last="Xue">Lu Xue</name><affiliation><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></affiliation></author><author><name sortKey="Tan, Li" sort="Tan, Li" uniqKey="Tan L" first="Li" last="Tan">Li Tan</name><affiliation><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></affiliation></author><author><name sortKey="Sai, Wen Bo" sort="Sai, Wen Bo" uniqKey="Sai W" first="Wen-Bo" last="Sai">Wen-Bo Sai</name><affiliation><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></affiliation></author><author><name sortKey="Liu, Xiao Cao" sort="Liu, Xiao Cao" uniqKey="Liu X" first="Xiao-Cao" last="Liu">Xiao-Cao Liu</name><affiliation><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></affiliation></author><author><name sortKey="Jiang, Qiu Ju" sort="Jiang, Qiu Ju" uniqKey="Jiang Q" first="Qiu-Ju" last="Jiang">Qiu-Ju Jiang</name><affiliation><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></affiliation></author><author><name sortKey="Shen, Jinhua" sort="Shen, Jinhua" uniqKey="Shen J" first="Jinhua" last="Shen">Jinhua Shen</name><affiliation><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></affiliation></author><author><name sortKey="Peng, Yong Bo" sort="Peng, Yong Bo" uniqKey="Peng Y" first="Yong-Bo" last="Peng">Yong-Bo Peng</name><affiliation><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></affiliation></author><author><name sortKey="Zhao, Ping" sort="Zhao, Ping" uniqKey="Zhao P" first="Ping" last="Zhao">Ping Zhao</name><affiliation><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></affiliation></author><author><name sortKey="Yu, Meng Fei" sort="Yu, Meng Fei" uniqKey="Yu M" first="Meng-Fei" last="Yu">Meng-Fei Yu</name><affiliation><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></affiliation></author><author><name sortKey="Chen, Weiwei" sort="Chen, Weiwei" uniqKey="Chen W" first="Weiwei" last="Chen">Weiwei Chen</name><affiliation><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></affiliation></author><author><name sortKey="Ma, Li Qun" sort="Ma, Li Qun" uniqKey="Ma L" first="Li-Qun" last="Ma">Li-Qun Ma</name><affiliation><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></affiliation></author><author><name sortKey="Zhai, Kui" sort="Zhai, Kui" uniqKey="Zhai K" first="Kui" last="Zhai">Kui Zhai</name><affiliation><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zou, Chunbin" sort="Zou, Chunbin" uniqKey="Zou C" first="Chunbin" last="Zou">Chunbin Zou</name><affiliation><nlm:affiliation>Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Donglin" sort="Guo, Donglin" uniqKey="Guo D" first="Donglin" last="Guo">Donglin Guo</name><affiliation><nlm:affiliation>Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Qin, Gangjian" sort="Qin, Gangjian" uniqKey="Qin G" first="Gangjian" last="Qin">Gangjian Qin</name><affiliation><nlm:affiliation>Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Yun Min" sort="Zheng, Yun Min" uniqKey="Zheng Y" first="Yun-Min" last="Zheng">Yun-Min Zheng</name><affiliation><nlm:affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Yong Xiao" sort="Wang, Yong Xiao" uniqKey="Wang Y" first="Yong-Xiao" last="Wang">Yong-Xiao Wang</name><affiliation><nlm:affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Guangju" sort="Ji, Guangju" uniqKey="Ji G" first="Guangju" last="Ji">Guangju Ji</name><affiliation><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Qing Hua" sort="Liu, Qing Hua" uniqKey="Liu Q" first="Qing-Hua" last="Liu">Qing-Hua Liu</name><affiliation><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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25822280</idno><idno type="pmid">25822280</idno><idno type="doi">10.1371/journal.pone.0121566</idno><idno type="wicri:Area/PubMed/Corpus">000261</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000261</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.</title><author><name sortKey="Wei, Ming Yu" sort="Wei, Ming Yu" uniqKey="Wei M" first="Ming-Yu" last="Wei">Ming-Yu Wei</name><affiliation><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></affiliation></author><author><name sortKey="Xue, Lu" sort="Xue, Lu" uniqKey="Xue L" first="Lu" last="Xue">Lu Xue</name><affiliation><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></affiliation></author><author><name sortKey="Tan, Li" sort="Tan, Li" uniqKey="Tan L" first="Li" last="Tan">Li Tan</name><affiliation><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></affiliation></author><author><name sortKey="Sai, Wen Bo" sort="Sai, Wen Bo" uniqKey="Sai W" first="Wen-Bo" last="Sai">Wen-Bo Sai</name><affiliation><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></affiliation></author><author><name sortKey="Liu, Xiao Cao" sort="Liu, Xiao Cao" uniqKey="Liu X" first="Xiao-Cao" last="Liu">Xiao-Cao Liu</name><affiliation><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></affiliation></author><author><name sortKey="Jiang, Qiu Ju" sort="Jiang, Qiu Ju" uniqKey="Jiang Q" first="Qiu-Ju" last="Jiang">Qiu-Ju Jiang</name><affiliation><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></affiliation></author><author><name sortKey="Shen, Jinhua" sort="Shen, Jinhua" uniqKey="Shen J" first="Jinhua" last="Shen">Jinhua Shen</name><affiliation><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></affiliation></author><author><name sortKey="Peng, Yong Bo" sort="Peng, Yong Bo" uniqKey="Peng Y" first="Yong-Bo" last="Peng">Yong-Bo Peng</name><affiliation><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></affiliation></author><author><name sortKey="Zhao, Ping" sort="Zhao, Ping" uniqKey="Zhao P" first="Ping" last="Zhao">Ping Zhao</name><affiliation><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></affiliation></author><author><name sortKey="Yu, Meng Fei" sort="Yu, Meng Fei" uniqKey="Yu M" first="Meng-Fei" last="Yu">Meng-Fei Yu</name><affiliation><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></affiliation></author><author><name sortKey="Chen, Weiwei" sort="Chen, Weiwei" uniqKey="Chen W" first="Weiwei" last="Chen">Weiwei Chen</name><affiliation><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></affiliation></author><author><name sortKey="Ma, Li Qun" sort="Ma, Li Qun" uniqKey="Ma L" first="Li-Qun" last="Ma">Li-Qun Ma</name><affiliation><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></affiliation></author><author><name sortKey="Zhai, Kui" sort="Zhai, Kui" uniqKey="Zhai K" first="Kui" last="Zhai">Kui Zhai</name><affiliation><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zou, Chunbin" sort="Zou, Chunbin" uniqKey="Zou C" first="Chunbin" last="Zou">Chunbin Zou</name><affiliation><nlm:affiliation>Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Donglin" sort="Guo, Donglin" uniqKey="Guo D" first="Donglin" last="Guo">Donglin Guo</name><affiliation><nlm:affiliation>Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Qin, Gangjian" sort="Qin, Gangjian" uniqKey="Qin G" first="Gangjian" last="Qin">Gangjian Qin</name><affiliation><nlm:affiliation>Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Yun Min" sort="Zheng, Yun Min" uniqKey="Zheng Y" first="Yun-Min" last="Zheng">Yun-Min Zheng</name><affiliation><nlm:affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Yong Xiao" sort="Wang, Yong Xiao" uniqKey="Wang Y" first="Yong-Xiao" last="Wang">Yong-Xiao Wang</name><affiliation><nlm:affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Guangju" sort="Ji, Guangju" uniqKey="Ji G" first="Guangju" last="Ji">Guangju Ji</name><affiliation><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Qing Hua" sort="Liu, Qing Hua" uniqKey="Liu Q" first="Qing-Hua" last="Liu">Qing-Hua Liu</name><affiliation><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></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><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="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Large-Conductance Calcium-Activated Potassium Channels</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Calcium Channel Blockers</term><term>Chloroquine</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Trachea</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Calcium Signaling</term><term>Muscle Contraction</term><term>Muscle, Smooth</term><term>Myocytes, Smooth Muscle</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Large-Conductance Calcium-Activated Potassium Channels</term><term>Muscle Contraction</term><term>Muscle, Smooth</term><term>Myocytes, Smooth Muscle</term><term>Ryanodine Receptor Calcium Release Channel</term><term>Trachea</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>In Vitro Techniques</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Patch-Clamp Techniques</term></keywords></textClass></profileDesc></teiHeader><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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25822280</PMID><DateCompleted><Year>2016</Year><Month>04</Month><Day>18</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>3</Issue><PubDate><Year>2015</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Involvement of large-conductance Ca2+-activated K+ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle.</ArticleTitle><Pagination><MedlinePgn>e0121566</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0121566</ELocationID><Abstract><AbstractText>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. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Ming-Yu</ForeName><Initials>MY</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xue</LastName><ForeName>Lu</ForeName><Initials>L</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sai</LastName><ForeName>Wen-Bo</ForeName><Initials>WB</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Xiao-Cao</ForeName><Initials>XC</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Qiu-Ju</ForeName><Initials>QJ</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Jinhua</ForeName><Initials>J</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Yong-Bo</ForeName><Initials>YB</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Ping</ForeName><Initials>P</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Meng-Fei</ForeName><Initials>MF</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Weiwei</ForeName><Initials>W</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Li-Qun</ForeName><Initials>LQ</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhai</LastName><ForeName>Kui</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Chunbin</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Donglin</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qin</LastName><ForeName>Gangjian</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Yun-Min</ForeName><Initials>YM</Initials><AffiliationInfo><Affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yong-Xiao</ForeName><Initials>YX</Initials><AffiliationInfo><Affiliation>Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ji</LastName><ForeName>Guangju</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Qing-Hua</ForeName><Initials>QH</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 HL108232</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL122865</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>03</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002121">Calcium Channel Blockers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051036">Large-Conductance Calcium-Activated Potassium Channels</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019837">Ryanodine 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