Native small airways secrete bicarbonate

Am J Respir Cell Mol Biol. 2014 Apr;50(4):796-804. doi: 10.1165/rcmb.2013-0418OC.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Bicarbonates / metabolism*
  • Calcium / metabolism
  • Chloride Channels / metabolism
  • Cyclic AMP / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Electric Conductivity
  • Female
  • Ion Transport
  • Lung / anatomy & histology*
  • Lung / drug effects
  • Lung / metabolism*
  • Male
  • Purinergic Agonists / pharmacology
  • Swine
  • Time Factors


  • Adrenergic beta-Agonists
  • Bicarbonates
  • Chloride Channels
  • Purinergic Agonists
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP
  • Calcium