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Bicarbonate‐dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu‐3

•  The mechanisms of anion and fluid transport by airway submucosal glands are not well understood and may differ from those in surface epithelium. •  The Calu‐3 cell line is often used as a model for submucosal gland serous cells and has cAMP‐stimulated fluid secretion; however, it does not actively transport chloride under short‐circuit conditions. •  In this study we show that fluid secretion requires chloride, bicarbonate and sodium, that chloride is the predominant anion in Calu‐3 secretions, and that a large fraction of the basolateral chloride loading during cAMP stimulation occurs by Cl−/HCO3− exchange. •  The results suggest a novel cellular model for anion and fluid secretion by Calu‐3 and submucosal gland acinar cells