Mechanism of control of Na,K-ATPase in principal cells of the mammalian collecting duct.
The collecting duct is the site of final Na reabsorption according to Na balance requirements. Using isolated rat cortical collecting ducts (CCD) and mpkCCD(cl4) cells, a mouse cortical collecting duct cell line, we have studied the physiological control of Na,K-ATPase, the key enzyme that energizes Na reabsorption. Aldosterone, a major regulator of Na transport by the collecting duct, stimulates Na,K-ATPase activity through both recruitment of intracellular pumps and increased total amounts of Na pump subunits. This effect is observed after a lag time of 1 hour and is independent of Na entry through ENaC, but requires de novo transcription and translation. Vasopressin and cAMP, its second messenger, stimulate Na,K-ATPase activity within minutes through translocation of Na pumps from a brefeldin A-sensitive intracellular pool to the plasma membrane. Dysregulation of collecting duct Na,K-ATPase activity is at least in part responsible of the Na retention observed in nephritic syndrome. In this setting, Na,K-ATPase activity and subunit synthesis are specifically increased in CCD. In conclusion, aldosterone, vasopressin, and intracellular Na control the cell surface expression of Na,K-ATPase and translocation from intracellular stores is a major mechanism of regulation of Na,K-ATPase activity in collecting duct principal cells.
Féraille
Eric
E
Division de Néphrologie, Fondation pour Recherches Médicales, CH-1211 Genève 4, Switzerland. Eric.Feraille@medecine.unige.ch
Mordasini
David
D
Gonin
Sandrine
S
Deschênes
Georges
G
Vinciguerra
Manlio
M
Doucet
Alain
A
Vandewalle
Alain
A
Summa
Vanessa
V
Verrey
François
F
Martin
Pierre-Yves
PY
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000201:enzymology / Q000502:physiology*; D008322:Mammals; D008954:Models, Biological; D009404:Nephrotic Syndrome / Q000201:enzymology / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D000450:Aldosterone; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase