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Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle

Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca(2+) channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We...

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Detalles Bibliográficos
Autores principales: Zhang, Ting, Luo, Xiao-Jing, Sai, Wen-Bo, Yu, Meng-Fei, Li, Wen-Er, Ma, Yun-Fei, Chen, Weiwei, Zhai, Kui, Qin, Gangjian, Guo, Donglin, Zheng, Yun-Min, Wang, Yong-Xiao, Shen, Jin-Hua, Ji, Guangju, Liu, Qing-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081631/
https://www.ncbi.nlm.nih.gov/pubmed/24992312
http://dx.doi.org/10.1371/journal.pone.0101578
Descripción
Sumario:Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca(2+) 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 Ca(2+) 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 Ca(2+)-free conditions, and, following a restoration of Ca(2+), 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 Ca(2+) elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.