Regulation of the Na+/K+ ATPase by Klotho

Klotho-hypomorphic (Klothohm) mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism. The present study explored the effect of Klotho on renal Na+/K+ ATPase activity. According to immunohistochemistry and confocal microscopy Na+/K+ ATPase protein abundance in isolated collecting ducts was lower in Klothohm mice than in their wild type littermates (Klotho(+/+)). Analysis with dual electrode voltage clamp recording showed that expression of Klotho in Xenopus oocytes increased the Na+/K+ ATPase pump current. Treatment of Xenopus oocytes with Klotho protein similarly increased the pump current. In conclusion, Klotho increases the membrane abundance and activity of the Na+/K+ ATPase. Decreased Na+/K+ ATPase activity could thus contribute to the volume-depletion of klothohm mice. Structured summary of protein interactions: Na+/K+ ATPase alpha-1 physically interacts with Klotho by anti bait coimmunoprecipitation (View interaction). (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.