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

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 Liu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Article numbere0121566
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 30 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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