Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance

Annu Rev Physiol. 1999;61:627-61. doi: 10.1146/annurev.physiol.61.1.627.


At birth, fetal distal lung epithelial (FDLE) cells switch from active chloride secretion to active sodium (Na+) reabsorption. Sodium ions enter the FDLE and alveolar type II (ATII) cells mainly through apical nonselective cation and Na(+)-selective channels, with conductances of 4-26 pS (picoSiemens) in FDLE and 20-25 pS in ATII cells. All these channels are inhibited by amiloride with a 50% inhibitory concentration of < 1 microM, and some are also inhibited by [N-ethyl-N-isopropyl]-2'-4'-amiloride (50% inhibitory concentration of < 1 microM). Both FDLE and ATII cells contain the alpha-, beta-, and gamma-rENaC (rat epithelial Na+ channels) mRNAs; reconstitution of an ATII cell Na(+)-channel protein into lipid bilayers revealed the presence of 25-pS Na+ single channels, inhibited by amiloride and [N-ethyl-N-isopropyl]-2'-4'-amiloride. A variety of agents, including cAMP, oxygen, glucocorticoids, and in some cases Ca2+, increased the activity and/or rENaC mRNA levels. The phenotypic properties of these channels differ from those observed in other Na(+)-absorbing epithelia. Pharmacological blockade of alveolar Na+ transport in vivo, as well as experiments with newborn alpha-rENaC knock-out mice, demonstrate the importance of active Na+ transport in the reabsorption of fluid from the fetal lung and in reabsorbing alveolar fluid in the injured adult lung. Indeed, in a number of inflammatory diseases, increased production of reactive oxygen-nitrogen intermediates, such as peroxynitrite (ONOO-), may damage ATII and FDLE Na+ channels, decrease Na+ reabsorption in vivo, and thus contribute to the formation of alveolar edema.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Biophysics
  • Cloning, Molecular
  • Epithelial Cells / metabolism
  • Gene Expression / physiology
  • Humans
  • Lung / metabolism
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism*
  • Sodium Channels / chemistry
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Sodium Channels / physiology


  • Sodium Channels