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PLoS One. 2015 Mar 30;10(3):e0121566. doi: 10.1371/journal.pone.0121566. eCollection 2015.

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

Author information

1
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.
2
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
3
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.
4
Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096, United States of America.
5
Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States of America.
6
Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States of America.

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.

PMID:
25822280
PMCID:
PMC4378962
DOI:
10.1371/journal.pone.0121566
[Indexed for MEDLINE]
Free PMC Article
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