title: Role of epithelial sodium channels in the regulation of lung fluid homeostasis.
abstract: 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 Ca(2+)-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.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Cell, Developmental, and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Pulmonary Injury and Repair Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Gregory Fleming James Cystic Fibrosis Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Bartoszewski
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Pulmonary Injury and Repair Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Gregory Fleming James Cystic Fibrosis Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and jcollawn@uab.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Collawn
mesh_terms: D001826:Body Fluids / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008168:Lung / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D053503:Epithelial Sodium Channels; D002794:Choline
keywords: oxidative stress; plasminogen activator; stem cells; steroid hormones; β-adrenergic agonists