Aldosterone acts via an ATP autocrine/paracrine system: The Edelman ATP hypothesis revisited

Julia Gorelik, Yanjun Zhang, Daniel Sánchez, Andrew Shevchuk, Gregory Frolenkov, Max Lab, David Klenerman, Christopher Edwards, Yuri Korchev

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Aldosterone, the most important sodium-retaining hormone, was first characterized > 50 years ago. However, despite numerous studies including the classical work of Isidore S. "Izzy" Edelman showing that aldosterone action depended on ATP production, the mechanism by which it activates sodium reabsorption via the epithelial sodium channel remains unclear. Here, we report experiments that suggest that one of the key steps in aldosterone action is via an autocrine/paracrine system. The hormone stimulates ATP release from the basolateral side of the target kidney cell. Prevention of ATP accumulation or its removal blocks aldosterone action. ATP then acts via a purinergic mechanism to produce contraction of small groups of adjacent epithelial cells. Patch clamping demonstrates that it is these contracted cells that have channel activity. With progressive recruitment of contracting cells, there is then a parallel increase in transepithelial electrical conductance. In common with other stimuli of sodium transport, this pathway involves phosphatidylinositol 3-kinase. Inhibition of phosphatidylinositol 3-kinase blocks both cell contraction and conductance. We put forward the hypothesis that redistribution of the cell volume caused by the lateral contraction results in apical swelling and that this change, in turn, disrupts the epithelial sodium channel interaction with the F-actin cytoskeleton, opening the channel and hence increasing sodium transport.

Original languageEnglish
Pages (from-to)15000-15005
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - Oct 18 2005


  • Epithelial sodium channel
  • Renal epithelium
  • Scanning ion conductance microscopy
  • Scanning probe microscopy

ASJC Scopus subject areas

  • General


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