title: Exposure to cigarette smoke condensate reduces calcium activated chloride channel transport in primary sinonasal epithelial cultures.
abstract: OBJECTIVE
  The cystic fibrosis transmembrane conductance regulator (CFTR) serves as a predominant Cl(-) transport conduit in airway epithelium and is inhibited by cigarette smoke in vitro and in vivo. Activation of secondary Cl(-) transport pathways through calcium-activated Cl(-) channels (CaCC) has been postulated as a mechanism to bypass defects in CFTR-mediated transport. Because it is not known whether CaCCs are also inhibited by tobacco exposure, the current study was designed to investigate the effect of cigarette smoke condensate (CSC) on CaCC transport.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  Well-characterized primary murine nasal septal epithelial (MNSE) and human sinonasal epithelial (HSNE) cultures were exposed to CSC in Ussing chambers. We monitored CaCC short-circuit current through stimulation of P2Y purinergic receptors with uridine triphosphate or adenosine triphosphate and selective inhibition of the CFTR-dependent secretory pathway. Characterization of CaCC current was also accomplished in primary airway cells derived from transgenic CFTR(-/-) (knockout) murine models.
  
  
  RESULTS
  Change in CaCC-mediated current (DeltaI(SC) representing transepithelial Ca-mediated Cl(-) secretion in muA/cm(2)) was significantly decreased in CSC-exposed wild type MNSE when compared to controls (32.8 +/- 4.6 vs. 47.5 +/- 2.3; respectively; P < .02). A similar effect was demonstrated in CFTR(-/-) MNSE cultures (33.4 +/- 2.8 vs. 38.6 +/- 2.0; P < .05>. HSNE cultures also had a significant reduction in I(SC) (16.1 +/- 0.6 vs. 22.7 +/- 0; P = .008).
  
  
  CONCLUSIONS
  CSC affects multiple pathways fundamental to airway ion transport, including both cyclic adenosine monophosphate and calcium activated Cl(-) transport. Inhibition of Cl(-) transport may contribute to common diseases of the airways, such as chronic rhinosinusitis and chronic obstructive pulmonary disease.
authors.affiliation: Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Alabama 35294, USA.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Virgin
authors.forename: Christopher
authors.initials: C
authors.lastname: Azbell
authors.forename: Daniel
authors.initials: D
authors.lastname: Schuster
authors.forename: Jumin
authors.initials: J
authors.lastname: Sunde
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Woodworth
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D051379:Mice; D008810:Mice, Inbred C57BL; D009079:Mucociliary Clearance / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D012907:Smoking
chemical_list: D018118:Chloride Channels; D000242:Cyclic AMP