Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC3

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

Authors: 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

Journal, date & volume: PLoS ONE, 2014 , 9, e101578

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24992312

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-induced 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.