Role of epithelial sodium channels in the regulation of lung fluid homeostasis

Academic Article


  • In utero, fetal lung epithelial cells actively secrete Cl- ions into the lung air spaces while Na+ ions follow passively to maintain electroneutrality. This process, driven by an electrochemical gradient generated by the Na+-K+-ATPase, is responsible for the secretion of fetal fluid that is essential for normal lung development. Shortly before birth, a significant upregulation of amiloride-sensitive epithelial channels (ENaCs) on the apical side of the lung epithelial cells results in upregulation of active Na+ transport. This process is critical for the reabsorption of fetal lung fluid and the establishment of optimum gas exchange. In the adult lung, active Na+ reabsorption across distal lung epithelial cells limits the degree of alveolar edema in patients with acute lung injury and cardiogenic edema. Cl- ions are transported either paracellularly or transcellularly to preserve electroneutrality. An increase in Cl- secretion across the distal lung epithelium has been reported following an acute increase in left atrial pressure and may result in pulmonary edema. In contrast, airway epithelial cells secrete Cl- through apical cystic fibrosis transmembrane conductance regulator and Ca2+-activated Cl- channels and absorb Na+. Thus the coordinated action of Cl- secretion and Na+ absorption is essential for maintenance of the volume of epithelial lining fluid that, in turn, maximizes mucociliary clearance and facilitates clearance of bacteria and debris from the lungs. Any factor that interferes with Na+ or Cl- transport or dramatically upregulates ENaC activity in airway epithelial cells has been associated with lung diseases such as cystic fibrosis or chronic obstructive lung disease. In this review we focus on the role of the ENaC, the mechanisms involved in ENaC regulation, and how ENaC dysregulation can lead to lung pathology.
  • Digital Object Identifier (doi)

    Author List

  • Matalon S; Bartoszewski R; Collawn JF
  • Start Page

  • L1229
  • End Page

  • L1238
  • Volume

  • 309
  • Issue

  • 11