title: Epithelial sodium channels in the adult lung--important modulators of pulmonary health and disease.
abstract: Absorption of excess fluid from the airways and alveolar lumen requires active vectorial transepithelial transport of sodium ions (Na+) by alveolar type II and possibly type I cells. The rate-limiting step in this process is the activity of the heterotrimeric apical membrane epithelial Na+ channel (ENaC). Pharmacologic inhibitors and genetic manipulations that disrupt Na+ transport result in fluid accumulation within the lung and failure of gas exchange. The importance of Na+ transport in the lung is also demonstrated in conditions such as ARDS, where abnormal absorption of Na+ contributes to the pathophysiology of pulmonary disease. ENaC expression and function is influenced by diverse factors, such as oxygen tension, glucocorticoids, and cytoskeletal proteins. In addition, ENaC dysfunction has been shown to be induced by purinergic nucleotide activation of P2Y receptors (in paramyxoviral bronchiolitis) and reactive species (in acute lung injury). Finally, beta-adrenergic agonists have been shown experimentally to reverse defects in ENaC function, and improve hypoxemia and pulmonary edema, and may provide a novel therapeutic modality for ARDS, although some viral lung pathogens appear to induce insensitivity to their actions.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Davis
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D053503:Epithelial Sodium Channels / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology*; D012307:Risk Factors; D012964:Sodium / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D053503:Epithelial Sodium Channels; D012964:Sodium