Journal Article

Native Small Airways Secrete Bicarbonate

Shamsuddin, A. K. M., Quinton, Paul M.

2014

Overview

Since the discovery of Cl(-) impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl(-) transport. However, loss of bicarbonate (HCO3(-)) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3(-) transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3(-) secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3(-) transport in native porcine small airways (∼ 1 mm φ). We assayed HCO3(-) transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3(-) plus 125-mM NaGlu Ringer's solution in the presence of luminal amiloride (10 μM). Under these conditions, because no major transportable anions other than HCO3(-) were present, we took the equivalent short-circuit current to be a direct measure of active HCO3(-) secretion. Applying selective agonists and inhibitors, we show constitutive HCO3(-) secretion in small airways, which can be stimulated significantly by β-adrenergic- (cAMP) and purinergic (Ca(2+)) -mediated agonists, independently. These results indicate that two separate components for HCO3(-) secretion, likely via CFTR- and calcium-activated chloride channel-dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways.

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Adrenergic beta-Agonists - pharmacology / Animals / Bicarbonates - metabolism / Calcium - metabolism / Chloride Channels - metabolism / Colleges & universities / Cyclic AMP - metabolism / Cystic fibrosis / Cystic Fibrosis Transmembrane Conductance Regulator - metabolism / Electric Conductivity / Female / Ion Transport / Lung - anatomy & histology / Lung - drug effects / Lung - metabolism / Lung - secretion / Male / Mortality / Original Research / Purinergic Agonists - pharmacology / Swine / Time Factors