title: Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle.
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.
authors.affiliation: 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, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 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, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: 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, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Sai
authors.affiliation: 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, China.
authors.forename: Meng-Fei
authors.initials: MF
authors.lastname: Yu
authors.affiliation: 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, China.
authors.forename: Wen-Er
authors.initials: WE
authors.lastname: Li
authors.affiliation: 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, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Ma
authors.affiliation: 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, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhai
authors.affiliation: Department of Medicine-Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
authors.affiliation: 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, China; Lankenau Institute for Medical Research & Main Line Health Heart Center, Wynnewood, Pennsylvania, United States of America.
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, United States of America.
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Zheng
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, United States of America.
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Wang
authors.affiliation: 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, China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Shen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
authors.affiliation: 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, China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D020746:Calcium Channels, L-Type; D007473:Ion Channels; D015221:Potassium Channels; D011720:Pyrazoles; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D002738:Chloroquine; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium