Question: 

During recent years there is increasing evidence for the presence of functional nicotinic acetylcholine receptors (nAChR) in airway epithelium. However, until now their role in this tissue is not fully understood. Therefore, the aim of this study was to investigate the influence of nicotine on transepithelial ion current in mouse tracheal epithelium.

Methodology: 

To investigate the nicotine-evoked ion current changes, electrophysiological Ussing-chamber recordings of mouse tracheal epithelium were employed.

Results: 

Application of nicotine (100 mM, apical) led to a transient current increase that was abolished in the presence of the nAChR antagonist mecamylamine (25 mM, apical) and reduced by the Cl^--channel inhibitor niflumic acid (100 mM, apical) or the K⁺-channel blocker BaCl₂ (5 mM, basolateral). Removal of apical Ca²⁺ did not influence the nicotine-evoked current, whereas the inosotol-1,4,5-triphosphate receptor antagonist 2-aminoethyl-diphenyl-borinate (75 mM, apical) and the Ca²⁺-ionophore A23187 (2 mM, apical) reduced the nicotine-effect. This indicates involvement of Ca²⁺-release from intracellular stores. Additionally, increasing intracellular cAMP by application of the cAMP-modulators 3-Isobutyl-1-methylxanthine (100 mM, apical) and forskolin (2 mM, apical) reduced the nicotine-effect. Further, the inhibitor of soluble adenylyl cyclase KH7 (10 mM, apical and basolateral) reduced the nicotine-induced current.

Conclusion: 

These results show that activation of nAChR by nicotine evokes an apical Cl^--secretion that is driven by basolateral K⁺-channels and dependent on Ca²⁺ and cAMP. The increase of intracellular cAMP is mediated by soluble adenylyl cyclase. These findings might be important for regulation of transepithelial ion transport and with this the regulation of the mucociliary clearance.