CFTR Dependent Bicarbonate Secretion in Native Small Airway Epithelia

Abstract

Loss of bicarbonate (HCO3−) transport may play a major role in pathological changes in airways, especially in Cystic Fibrosis (CF). In the small intestine normal mucus release requires CFTR dependent HCO3− secretion. HCO3− may also be crucial for effective bactericidal activities of antibiotics as well as innate antimicrobials. Evidence indicates that HCO3− secretion is present in normal, but defective in CF cultured airway cells. However, whether HCO3− is secreted in native small airways is not known. We have developed a mini‐Ussing system and assayed HCO3− transport in native small airways of pigs and humans indirectly as the changes of transepithelial potential and equivalent short circuit current. With bilateral 25 mM NaHCO3− plus 125 mM NaGlu Ringers’ with amiloride in the lumen, we stimulated with different cAMP and Ca2+ mediated agonists and inhibited with known blockers of HCO3− transport. Results showed that the native small airway epithelia are capable of secreting CFTR dependent HCO3−. HCO3− secretion is physiologically regulated, and probably critical to normal innate defense mechanism of the airways. Failure to secrete HCO3− may cause poor mucociliary and pathogen clearance and may be a target for therapy.Supported by the Nancy Olmsted Trust, NIH (R01‐HL084042) and Cystic Fibrosis Foundation.