title: Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.
abstract: Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.
authors.affiliation: Departments of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Yim
authors.forename: George
authors.initials: G
authors.lastname: Gallos
authors.forename: Jose F
authors.initials: JF
authors.lastname: Perez-Zoghbi
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Trice
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Matthew
authors.initials: M
authors.lastname: Siviski
authors.forename: Joshua
authors.initials: J
authors.lastname: Sonett
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
mesh_terms: D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D009544:Niflumic Acid / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
chemical_list: D018118:Chloride Channels; D026902:Potassium Channel Blockers; D009544:Niflumic Acid; D019789:Tetraethylammonium