Airway epithelial cells-Functional links between CFTR and anoctamin dependent Cl− secretion

Airways consist of a heterogeneous population of cells, comprising ciliated cells, Clara cells and goblet cells. Electrolyte secretion by the airways is necessary to produce the airway surface liquid that allows for mucociliary clearance of the lungs. Secretion is driven by opening of Cl− selective ion channels in the apical membrane of airway epithelial cells, through either receptor mediated increase in intracellular cAMP or cytosolic Ca2+. Traditionally cAMP-dependent and Ca2+-dependent secretory pathways are regarded as independent. However, this concept has been challenged recently. With identification of the Ca2+ activated Cl− channel TMEM16A (anoctamin 1) and with detailed knowledge of the cAMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR), it has become possible to look more closely into this relationship.