CFTR Dependent Bicarbonate Secretion in Native Small Airway Epithelia

Loss of bicarbonate (HCO 3 − ) 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 HCO 3 − secretion. HCO 3 − may also be crucial for effective bactericidal activities of antibiotics as well as innate antimicrobials. Evidence indicates that HCO 3 − secretion is present in normal, but defective in CF cultured airway cells. However, whether HCO 3 − is secreted in native small airways is not known. We have developed a mini‐Ussing system and assayed HCO 3 − 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 NaHCO 3 − plus 125 mM NaGlu Ringers’ with amiloride in the lumen, we stimulated with different cAMP and Ca 2+ mediated agonists and inhibited with known blockers of HCO 3 − transport. Results showed that the native small airway epithelia are capable of secreting CFTR dependent HCO 3 − . HCO 3 − secretion is physiologically regulated, and probably critical to normal innate defense mechanism of the airways. Failure to secrete HCO 3 − 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.