Structural mechanisms underlying the function of epithelial sodium channel/acid-sensing ion channel

Curr Opin Nephrol Hypertens. 2011 Sep;20(5):555-60. doi: 10.1097/MNH.0b013e328348bcac.


Purpose of review: The epithelial sodium channel/degenerin family encompasses a group of cation-selective ion channels that are activated or modulated by a variety of extracellular stimuli. This review describes findings that provide new insights into the molecular mechanisms that control the function of these channels.

Recent findings: Epithelial sodium channels facilitate Na⁺ reabsorption in the distal nephron and hence have a role in fluid volume homeostasis and arterial blood pressure regulation. Acid-sensing ion channels are broadly distributed in the nervous system where they contribute to the sensory processes. The atomic structure of acid-sensing ion channel 1 illustrates the complex trimeric architecture of these proteins. Each subunit has two transmembrane spanning helices, a highly organized ectodomain and intracellular N-terminus and C-terminus. Recent findings have begun to elucidate the structural elements that allow these channels to sense and respond to extracellular factors. This review emphasizes the roles of the extracellular domain in sensing changes in the extracellular milieu and of the residues in the extracellular-transmembrane domains interface in coupling extracellular changes to the pore of the channel.

Summary: Epithelial sodium channels and acid-sensing ion channels have evolved to sense extracellular cues. Future research should be directed toward elucidating how changes triggered by extracellular factors translate into pore opening and closing events.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acid Sensing Ion Channels
  • Animals
  • Degenerin Sodium Channels
  • Epithelial Cells / metabolism*
  • Epithelial Sodium Channels / chemistry
  • Epithelial Sodium Channels / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Kidney / metabolism*
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Protein Conformation
  • Sodium / metabolism*
  • Sodium Channels / chemistry
  • Sodium Channels / metabolism*
  • Structure-Activity Relationship


  • ASIC2 protein, human
  • Acid Sensing Ion Channels
  • Degenerin Sodium Channels
  • Epithelial Sodium Channels
  • Nerve Tissue Proteins
  • Sodium Channels
  • Sodium