Na+/K+-ATPase is expressed abundantly in the kidneys. Expression is highest in the thick ascending limb of the loop of Henle (TAL) and the distal convoluted tubule, intermediate in the proximal tubule, relatively low in the collecting ducts and extremely low in the thin limb of loop of Henle. In the normal kidney it is located exclusively in the basolateral membranes, closely surrounded by mitochondria. Na+/K+-ATPase is comprised of α and β subunits in 1:1 ratio which are both essential. The α1 isoform is expressed in kidneys. It is the catalytic subunit and has binding sites for ATP, Na+, K+ and ouabain. The β subunit is essential for folding, stabilizing and membrane targeting. Sometimes a ƴ subunit is also incorporated but it is not an absolute requirement.
Na+/K+-ATPase hydrolyses ATP to pump 3 Na+ ions out and 2 K+ into cells. It is stimulated by Na+. Since this occurs at well-below the Vmax in intact cells, any increase in intracellular Na+ increases activity. On the extracellular side it is stimulated by K+ (Km 0.5–1.5 mM). K+ is only rate-limiting in severe hypokalemia. Lithium stimulates activity but not at physiological concentrations. Activity is under hormonal control. In the proximal tubule, it is stimulated by AII (if bicarbonate is ≥ 20 mM), α1 and β stimulation by epinephrine and norepinephrine, and insulin, and is inhibited by dopamine, PTH and PTH-related peptide.
