title: Intracellular Na+ controls cell surface expression of Na,K-ATPase via a cAMP-independent PKA pathway in mammalian kidney collecting duct cells.
abstract: In the mammalian kidney the fine control of Na+ reabsorption takes place in collecting duct principal cells where basolateral Na,K-ATPase provides the driving force for vectorial Na+ transport. In the cortical collecting duct (CCD), a rise in intracellular Na+ concentration ([Na+]i) was shown to increase Na,K-ATPase activity and the number of ouabain binding sites, but the mechanism responsible for this event has not yet been elucidated. A rise in [Na+]i caused by incubation with the Na+ ionophore nystatin, increased Na,K-ATPase activity and cell surface expression to the same extent in isolated rat CCD. In cultured mouse mpkCCDcl4 collecting duct cells, increasing [Na+]i either by cell membrane permeabilization with amphotericin B or nystatin, or by incubating cells in a K(+)-free medium, also increased Na,K-ATPase cell surface expression. The [Na+]i-dependent increase in Na,K-ATPase cell-surface expression was prevented by PKA inhibitors H89 and PKI. Moreover, the effects of [Na+]i and cAMP were not additive. However, [Na+]i-dependent activation of PKA was not associated with an increase in cellular cAMP but was prevented by inhibiting the proteasome. These findings suggest that Na,K-ATPase may be recruited to the cell membrane following an increase in [Na+]i through cAMP-independent PKA activation that is itself dependent on proteasomal activity.
authors.affiliation: Division de Néphrologie, Fondation pour Recherches Médicales, CH-1211 Genève 4, Switzerland.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Udo
authors.initials: U
authors.lastname: Hasler
authors.forename: David
authors.initials: D
authors.lastname: Mordasini
authors.forename: Martine
authors.initials: M
authors.lastname: Rousselot
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.forename: Alain
authors.initials: A
authors.lastname: Vandewalle
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009761:Nystatin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013449:Sulfonamides
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D007546:Isoquinolines; D013449:Sulfonamides; C028996:cardiac glycoside receptors; D009761:Nystatin; D000666:Amphotericin B; D012964:Sodium; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D011188:Potassium