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Potassium acts through mTOR to regulate its own secretion

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  • Mads Vaarby Sørensen
  • Bidisha Saha, University of California, San Francisco
  • ,
  • Iben Skov Jensen
  • ,
  • Peng Wu, New York Medical College
  • ,
  • Niklas Ayasse
  • ,
  • Catherine E. Gleason, University of California, San Francisco
  • ,
  • Samuel Levi Svendsen
  • Wen Hui Wang, New York Medical College
  • ,
  • David Pearce, University of California, San Francisco

Potassium (K+) secretion by kidney tubule cells is central to electrolyte homeostasis in mammals. In the K+-secreting principal cells of the distal nephron, electrogenic Na+ transport by the epithelial sodium channel (ENaC) generates the electrical driving force for K+ transport across the apical membrane. Regulation of this process is attributable in part to aldosterone, which stimulates the gene transcription of the ENaC-regulatory kinase, SGK1. However, a wide range of evidence supports the conclusion that an unidentified aldosterone-independent pathway exists. We show here that in principal cells, K+ itself acts through the type 2 mTOR complex (mTORC2) to activate SGK1, which stimulates ENaC to enhance K+ excretion. The effect depends on changes in K+ concentration on the blood side of the cells, and requires basolateral membrane K+-channel activity. However, it does not depend on changes in aldosterone, or on enhanced distal delivery of Na+ from upstream nephron segments. These data strongly support the idea that K+ is sensed directly by principal cells to stimulate its own secretion by activating the mTORC2/SGK1 signaling module, and stimulate ENaC. We propose that this local effect acts in concert with aldosterone and increased Na+ delivery from upstream nephron segments to sustain K+ homeostasis.

Original languageEnglish
Article numbere126910
JournalJCI Insight
Number of pages18
Publication statusPublished - 2019

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