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

Wei, MY and Xue, L and Tan, L and Sai, WB and Liu, XC and Jiang, QJ and Shen, J and Peng, YB and Zhao, P and Yu, MF and Chen, W and Ma, LQ and Zhai, K and Zou, C and Guo, D and Qin, G and Zheng, YM and Wang, YX and Ji, G and Liu, QH (2015) Involvement of large-conductance Ca²⁺-activated K⁺ channels in chloroquine-induced force alterations in pre-contracted airway smooth muscle. PLoS ONE, 10 (3).

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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.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Wei, MY Xue, L Tan, L Sai, WB Liu, XC Jiang, QJ Shen, J Peng, YB Zhao, P Yu, MF Chen, W Ma, LQ Zhai, K Zou, C chz4@pitt.edu CHZ4 0000-0003-1355-4726 Guo, D Qin, G Zheng, YM Wang, YX Ji, G Liu, QH
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Hu, Wenhui UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	30 March 2015
Date Type:	Publication
Access Restriction:	No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title:	PLoS ONE
Volume:	10
Number:	3
DOI or Unique Handle:	10.1371/journal.pone.0121566
Institution:	University of Pittsburgh
Schools and Programs:	School of Medicine > Medicine
Refereed:	Yes
Date Deposited:	23 Aug 2016 14:00
Last Modified:	25 Jun 2021 19:55
URI:	http://d-scholarship.pitt.edu/id/eprint/28491

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