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Scientific article
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Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na,K-ATPase in collecting duct principal cells

Published inJournal of the American Society of Nephrology, vol. 25, no. 2, p. 250-259
Publication date2014
Abstract

In relation to dietary Na(+) intake and aldosterone levels, collecting duct principal cells are exposed to large variations in Na(+) transport. In these cells, Na(+) crosses the apical membrane via epithelial Na(+) channels (ENaC) and is extruded into the interstitium by Na,K-ATPase. The activity of ENaC and Na,K-ATPase must be highly coordinated to accommodate variations in Na(+) transport and minimize fluctuations in intracellular Na(+) concentration. We hypothesized that, independent of hormonal stimulus, cross-talk between ENaC and Na,K-ATPase coordinates Na(+) transport across apical and basolateral membranes. By varying Na(+) intake in aldosterone-clamped rats and overexpressing γ-ENaC or modulating apical Na(+) availability in cultured mouse collecting duct cells, enhanced apical Na(+) entry invariably led to increased basolateral Na,K-ATPase expression and activity. In cultured collecting duct cells, enhanced apical Na(+) entry increased the basolateral cell surface expression of Na,K-ATPase by inhibiting p38 kinase-mediated endocytosis of Na,K-ATPase. Our results reveal a new role for p38 kinase in mediating cross-talk between apical Na(+) entry via ENaC and its basolateral exit via Na,K-ATPase, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits.

Keywords
  • AMP-Activated Protein Kinases/physiology
  • Aldosterone/physiology
  • Animals
  • Basement Membrane/metabolism
  • Biological Transport, Active/physiology
  • Cell Line, Transformed
  • Cell Membrane/metabolism
  • Cell Polarity
  • Endocytosis/physiology
  • Enzyme Induction
  • Epithelial Sodium Channels/biosynthesis/genetics/physiology
  • Homeostasis/physiology
  • Intracellular Fluid/metabolism
  • Ion Transport/physiology
  • Kidney Tubules, Collecting/cytology/metabolism
  • Lysosomes/metabolism
  • MAP Kinase Signaling System/drug effects/physiology
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Sodium/metabolism
  • Sodium-Potassium-Exchanging ATPase/biosynthesis/genetics/metabolism/physiology
  • p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
Citation (ISO format)
WANG, Yu-Bao et al. Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na,K-ATPase in collecting duct principal cells. In: Journal of the American Society of Nephrology, 2014, vol. 25, n° 2, p. 250–259. doi: 10.1681/ASN.2013040429
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1046-6673
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