title: Avertin®, but Not Volatile Anesthetics Addressing the Two-Pore Domain K+ Channel, TASK-1, Slows Down Cilia-Driven Particle Transport in the Mouse Trachea.
abstract: BACKGROUND
  Volatile anesthetics inhibit mucociliary clearance in the airways. The two-pore domain K+ channel, TASK-1, represents one of their molecular targets in that they increase its open probability. Here, we determine whether particle transport speed (PTS) at the mucosal surface of the mouse trachea, an important factor of the cilia-driven mechanism in mucociliary clearance, is regulated by TASK-1.
  
  
  RESULTS
  RT-PCR analysis revealed expression of TASK-1 mRNA in the manually dissected and laser-assisted microdissected tracheal epithelium of the mouse. Effects of anesthetics (isoflurane and Avertin®) and TASK-1 inhibitors (anandamide and A293) on ciliary activity were investigated by assessment of PTS at the mucosal surface of the explanted and opened murine trachea. Neither TASK-1 inhibitors nor isoflurane had any impact on basal and ATP-stimulated PTS. Avertin® reduced basal PTS, and ATP-stimulated PTS decreased in its presence in wild-type (WT) mice. Avertin®-induced decrease in basal PTS persisted in WT mice in the presence of TASK-1 inhibitors, and in two different strains of TASK-1 knockout mice.
  
  
  CONCLUSIONS
  Our findings indicate that TASK-1 is expressed by the tracheal epithelium but is not critically involved in the regulation of tracheal PTS in mice. Avertin® reduces PTS independent of TASK-1.
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University and German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary System (ECCPS), Giessen, Germany.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Murtaza
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University and German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary System (ECCPS), Giessen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Mermer
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University and German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary System (ECCPS), Giessen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfeil
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University and German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary System (ECCPS), Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002923:Cilia / Q000187:drug effects*; D000431:Ethanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C062527:tribromoethanol; C420132:potassium channel subfamily K member 3; D000431:Ethanol