title: H2S relaxes isolated human airway smooth muscle cells via the sarcolemmal K(ATP) channel.
abstract: Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)-the end effector of acute airway narrowing in asthma. Using magnetic twisting cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1-10mM). GYY4137 slowly released appreciable levels of H2S in the range of 10-275 μM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Fitzgerald
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Breann
authors.initials: B
authors.lastname: DeSantiago
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Danielle Y
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Cardiovascular and Metabolic Research Unit, Lakehead University, Thunder Bay, ON, Canada.
authors.forename: Guangdong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: D Brian
authors.initials: DB
authors.lastname: Foster
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chan-Li
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Horton
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Airways Biology Initiative, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: san@jhsph.edu.
authors.forename: Steven S
authors.initials: SS
authors.lastname: An
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D001993:Bronchodilator Agents / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; C529376:GYY 4137; D054086:KATP Channels; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D013440:Sulfides; D020110:Pinacidil; D003542:Cystathionine gamma-Lyase; D005905:Glyburide; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: ATP-sensitive potassium channels; Airway smooth muscle; Asthma; H(2)S; Single cell contraction