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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / physiology
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Aldosterone / physiology
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Animals
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Basement Membrane / metabolism
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Biological Transport, Active / physiology
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Cell Line, Transformed
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Cell Membrane / metabolism
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Cell Polarity
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Endocytosis / physiology
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Enzyme Induction
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Epithelial Sodium Channels / biosynthesis
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Epithelial Sodium Channels / genetics
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Epithelial Sodium Channels / physiology*
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Homeostasis / physiology
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Intracellular Fluid / metabolism
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Ion Transport / physiology
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Kidney Tubules, Collecting / cytology
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Kidney Tubules, Collecting / metabolism*
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Lysosomes / metabolism
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Male
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Mice
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Rats
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Rats, Sprague-Dawley
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Sodium / metabolism*
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Sodium-Potassium-Exchanging ATPase / biosynthesis
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Sodium-Potassium-Exchanging ATPase / genetics
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Sodium-Potassium-Exchanging ATPase / metabolism
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Sodium-Potassium-Exchanging ATPase / physiology*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / physiology*
Substances
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Epithelial Sodium Channels
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Scnn1g protein, mouse
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Aldosterone
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Sodium
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p38 Mitogen-Activated Protein Kinases
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AMP-Activated Protein Kinases
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Atp1a1 protein, rat
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Atp1a2 protein, rat
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Atp1a1 protein, mouse
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Sodium-Potassium-Exchanging ATPase