Regulation of airway mucosal ion transport

The secretion of fluid into the airway lumen is due in part to active chloride secretion across the epithelium. Changes in Cl secretion require coordinated changes in the turnover of several transport proteins in order to avoid lethal changes in cell volume. Several different Ca- and cAMP-dependent pathways effect this coordination. Many mediators raise cyclic AMP which activates protein kinase A which in turn opens the apical membrane Cl channel. Cyclic AMP also raises Cai (without change in levels of inositol triphosphate, IP3), and this Ca is probably responsible for activation of basolateral K channels and NaK2Cl cotransporters. Other mediators raise Cai by elevating IP3, and seem to stimulate chloride secretion entirely by Ca-dependent pathways with no change in cyclic AMP levels. Protein kinase C and arachidonic acid inhibit Cl secretion.