title: Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na,K-ATPase in collecting duct principal cells.
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.
authors.affiliation: Service of Nephrology, Department of Cell Physiology and Metabolism, University Medical Center, Geneva, Switzerland;
authors.forename: Yu-Bao
authors.initials: YB
authors.lastname: Wang
authors.forename: Valérie
authors.initials: V
authors.lastname: Leroy
authors.forename: Arvid B
authors.initials: AB
authors.lastname: Maunsbach
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.forename: Udo
authors.initials: U
authors.lastname: Hasler
authors.forename: Eva
authors.initials: E
authors.lastname: Dizin
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernandez
authors.forename: Sophie
authors.initials: S
authors.lastname: de Seigneux
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology; D000450:Aldosterone / Q000502:physiology; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004705:Endocytosis / Q000502:physiology; D004790:Enzyme Induction; D053503:Epithelial Sodium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; C507053:Scnn1g protein, mouse; D000450:Aldosterone; D012964:Sodium; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C499075:Atp1a1 protein, rat; C498532:Atp1a2 protein, rat; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase