Premium
Exposure to cigarette smoke condensate reduces calcium activated chloride channel transport in primary sinonasal epithelial cultures
Author(s) -
Virgin Frank W.,
Azbell Christopher,
Schuster Daniel,
Sunde Jumin,
Zhang Shaoyan,
Sorscher Eric J.,
Woodworth Bradford A.
Publication year - 2010
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.20930
Subject(s) - cystic fibrosis transmembrane conductance regulator , chemistry , chloride channel , ussing chamber , purinergic receptor , ion transporter , adenosine , calcium , respiratory epithelium , medicine , endocrinology , secretion , microbiology and biotechnology , biochemistry , biology , respiratory system , organic chemistry , membrane , gene
Objectives/Hypothesis: 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. Study Design: 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 (ΔI SC representing transepithelial Ca‐mediated Cl − secretion in μA/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. Laryngoscope, 2010