Regulation of the Na⁺/K⁺ ATPase by Klotho

Klotho-hypomorphic (Klotho^hm) 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 Klotho^hm 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 klotho^hm mice.