Bicarbonate secretion is an essential physiological component of electrolyte transport in the small airways

Even though cystic fibrosis transmembrane conductance regulator (CFTR) mutations disrupt Cl − transport, major pathologies associated with cystic fibrosis (CF) appear to be closely associated with defective bicarbonate (HCO 3 − ) transport. Recent evidence indicates a direct link between the abnormal HCO 3 − ƒntransport and thickened mucus in multiple organ systems including the small airways in CF. We have developed a novel, physiologically viable model system to investigate HCO 3 − transport in the porcine native small airways and show for the first time that the small airways are capable of secreting HCO 3 − when stimulated by putative cAMP and Ca 2+ mediated agonists. With bilateral 25 mM HCO 3 − and apical, Fsk/IBMX, PGE2, and UTP acutely increased equivalent short circuit current (I sc eq ) significantly by 15.1 ± 2.3 (n=10), 27.0 ± 9.7 (n=3) and 8.3 ± 1.5 (n=5) μA/cm 2 respectively. Since no other permeable anion except HCO 3 − was present and since amiloride was present to block Na + transport, the increases in I sc eq indicate stimulation of cAMP and Ca 2+ mediated HCO 3 − secretion. Moreover, mucus discharge in isolated bronchioles stimulated with PGE2, histologically appear more expanded in the presence than in the absence of HCO 3 − . These results support the notion that HCO 3 − is critical for normal mucus release in the airway. Supported by the Nancy Olmsted Trust, NIH (R01‐ HL084042 ) and Cystic Fibrosis Foundation.