Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited

Physiol Rev. 2015 Jan;95(1):297-340. doi: 10.1152/physrev.00011.2014.


Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Publication types

  • Portrait
  • Review

MeSH terms

  • Aldosterone / metabolism*
  • Animals
  • Biological Evolution*
  • Epithelial Sodium Channels / chemistry
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism*
  • Genome, Human
  • Humans
  • Nephrons / physiology
  • Signal Transduction / physiology
  • Sodium / metabolism*
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Epithelial Sodium Channels
  • Aldosterone
  • Sodium
  • Sodium-Potassium-Exchanging ATPase