title: Cellular mechanism underlying hydrogen sulfide induced mouse tracheal smooth muscle relaxation: role of BKCa.
abstract: Recent studies have suggested that hydrogen sulfide (H2S), an important endogenous signaling gaseous molecule, participates in relaxation of smooth muscle. Nevertheless, the mechanism of this relaxation effect on respiratory system is still unclear. The present study aims to investigate the physiological function as well as cellular mechanism of H2S in tracheal smooth muscle. Application of the H2S donor, sodium hydrosulphide (NaHS) and the precursor of H2S, l-cysteine (l-Cys) induced mouse tracheal smooth muscle (TSM) relaxation in an epithelium-independent manner. The relaxation of TSM induced by NaHS was abrogated by iberiotoxin (IbTX), the large conductance calcium activated potassium channel (BKCa) blocker. In primary cultured mouse TSM cells, NaHS remarkably increased potassium outward currents in whole-cell patch clamp, hyperpolarized TSM cells and inhibited the calcium influx. All of these effects were significantly blocked by IbTX. Consistent with the results in vitro, administration of NaHS in vivo also reduced airway hyperresponsiveness in Ovalbumin (OVA)-challenged asthmatic mice. Our present study indicates that NaHS can induce mouse TSM relaxation by activating BKCa. These observations reveal the physiological function of H2S in airway, which provides a promising pharmacological target for the treatment of asthma and other respiratory diseases associated with over-contraction of TSM.
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Jiehong
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Yu-li
authors.initials: YL
authors.lastname: Luo
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Yi-lin
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Peng-xiao
authors.initials: PX
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China.
authors.forename: Jia-wen
authors.initials: JW
authors.lastname: Xu
authors.affiliation: State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou 510120, PR China.
authors.forename: Min-hui
authors.initials: MH
authors.lastname: Chen
authors.affiliation: State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou 510120, PR China.
authors.forename: Yong-feng
authors.initials: YF
authors.lastname: Luo
authors.affiliation: State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou 510120, PR China.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Zhong
authors.affiliation: State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou 510120, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, PR China. Electronic address: lsszwl2@aliyun.com.
authors.forename: Wen-liang
authors.initials: WL
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D006862:Hydrogen Sulfide
keywords: Asthma; BK(Ca) channels; H(2)S; H(2)S ( PubChem CID: 402); Tracheal smooth muscle