Regulation of the epithelial sodium channel (ENaC) by membrane trafficking

Biochim Biophys Acta. 2010 Dec;1802(12):1166-77. doi: 10.1016/j.bbadis.2010.03.010. Epub 2010 Mar 27.


The epithelial Na(+) channel (ENaC) is a major regulator of salt and water reabsorption in a number of epithelial tissues. Abnormalities in ENaC function have been directly linked to several human disease states including Liddle syndrome, psuedohypoaldosteronism, and cystic fibrosis and may be implicated in salt-sensitive hypertension. ENaC activity in epithelial cells is regulated both by open probability and channel number. This review focuses on the regulation of ENaC in the cells of the kidney cortical collecting duct by trafficking and recycling. The trafficking of ENaC is discussed in the broader context of epithelial cell vesicle trafficking. Well-characterized pathways and protein interactions elucidated using epithelial model cells are discussed, and the known overlap with ENaC regulation is highlighted. In following the life of ENaC in CCD epithelial cells the apical delivery, internalization, recycling, and destruction of the channel will be discussed. While a number of pathways presented still need to be linked to ENaC regulation and many details of the regulation of ENaC trafficking remain to be elucidated, knowledge of these mechanisms may provide further insights into ENaC activity in normal and disease states.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism*
  • Humans
  • Kidney Tubules, Collecting / metabolism*
  • Liddle Syndrome / genetics
  • Liddle Syndrome / metabolism
  • Protein Transport / genetics
  • Pseudohypoaldosteronism / genetics
  • Pseudohypoaldosteronism / metabolism


  • Epithelial Sodium Channels