Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle

Ting Zhang, Xiao Jing Luo, Wen Bo Sai, Meng Fei Yu, Wen Er Li, Yun Fei Ma, Weiwei Chen, Kui Zhai, Gangjian Qin, Donglin Guo, Yun Min Zheng, Yong Xiao Wang, Jin Hua Shen, Guangju Ji, Qing Hua Liu

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 μM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-nduced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

Original languageEnglish (US)
Article numbere101578
JournalPloS one
Volume9
Issue number7
DOIs
StatePublished - Jul 3 2014

ASJC Scopus subject areas

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

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