Fig. 1.

The respiratory tract: segments of the airways, cell types, and ion transport in epithelial cells. Na⁺ ions enter the cytoplasm of ciliated airway cells and alveolar type I (ATI) and type II (ATII) cells, through channels, down an electrochemical gradient, created by the energy-consuming, ouabain-sensitive Na⁺/K⁺-ATPase located at the basolateral surface. Two different types of Na⁺ channels have been identified. Highly selective Na⁺ channels, consisting of at least 3 subunits (α, β, and γ), which are inhibited by micromolar concentrations of amiloride (epithelial Na channels, ENaC) and nonselective cation channels, consisting of the α-subunit. K⁺ ions exit the cells via basolateral K⁺ channels (KC). Ciliated cells secrete Cl⁻ ions through cystic fibrosis transmembrane conductance regulator (CFTR), as well as Ca²⁺- activated Cl⁻ channels (CaCC) and SCL26A9. Cl⁻ ions enter the cells via the basolateral Na⁺/K⁺/2Cl⁻ (NKCC) symporter, down an electrochemical gradient created by the Na⁺/K⁺-ATPase. In alveolar cells, Cl⁻ transport across CFTR is likely bidirectional and depends on the concentration gradient. In ATII and ATI cells, Cl⁻ enters cells through CFTR or crosses across the paracellular junctions to maintain electroneutrality. PCL, pericilary fluid; ASL, airway surface fluid; ALF, alveolar lining fluid; AEC, airway epithelial cell.