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JCI Insight. 2019 Apr 23;5. pii: 126910. doi: 10.1172/jci.insight.126910.

Potassium acts through mTOR to regulate its own secretion.

Author information

1
Departments of Biomedicine and Physiology, Aarhus University, Aarhus, Denmark.
2
Aarhus Institute for Advanced Studies, Aarhus University, Aarhus, Denmark.
3
Department of Medicine, Division of Nephrology, and Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, California, USA.
4
Department of Pharmacology, New York Medical College, Valhalla, New York, USA.

Abstract

Potassium (K+) secretion by kidney tubule cells is central to electrolyte homeostasis in mammals. In the K+ secretory "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.

KEYWORDS:

Cell Biology; Homeostasis; Nephrology; Signal transduction; Sodium channels

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