Chloride secretion across adult alveolar epithelial cells contributes to cardiogenic edema

Abstract

In utero, fetal lung epithelial cells actively secrete chloride (Cl−) ions into the lung airspaces. Cl− ions enter the basolateral membranes through Na+/K+/2Cl− (NKCC) transporters (1), down an electrochemical gradient generated by the basolateral Na+/K+/ATPase, and exit through apical anion channels, including the cAMP- activated cystic fibrosis transmembrane regulator (CFTR) (2). Na+ ions follow passively through the paracellular junctions to preserve electroneutrality. The vectorial transport of NaCl generates an oncotic pressure, which drives fetal fluid secretion into the airway lumen. Shortly before birth, Cl− secretion diminishes and active Na+ transport begins: Na+ ions enter lung epithelial cells through amiloride-sensitive Na+ channels (ENaC) and are extruded across the basolateral membranes by the Na+/K+/ATPase (3, 4). This process is critical for the reabsorption of fetal lung fluid and the establishment of gas exchange. In the adult lung active Na+ reabsorption limits the degree of alveolar edema in hyperoxic lung injury (5) and in patients with acute respiratory distress syndrome (6, 7).