The renal H+-K+-ATPases: physiology, regulation, and structure

Abstract

The H⁺-K⁺-ATPases are ion pumps that use the energy of ATP hydrolysis to transport protons (H⁺) in exchange for potassium ions (K⁺). These enzymes consist of a catalytic α-subunit and a regulatory β-subunit. There are two catalytic subunits present in the kidney, the gastric or HKα₁isoform and the colonic or HKα₂isoform. In this review we discuss new information on the physiological function, regulation, and structure of the renal H⁺-K⁺-ATPases. Evaluation of enzymatic functions along the nephron and collecting duct and studies in HKα₁and HKα₂knockout mice suggest that the H⁺-K⁺-ATPases may function to transport ions other than protons and potassium. These reports and recent studies in mice lacking both HKα₁and HKα₂suggest important roles for the renal H⁺-K⁺-ATPases in acid/base balance as well as potassium and sodium homeostasis. Molecular modeling studies based on the crystal structure of a related enzyme have made it possible to evaluate the structures of HKα₁and HKα₂and provide a means to study the specific cation transport properties of H⁺-K⁺-ATPases. Studies to characterize the cation specificity of these enzymes under different physiological conditions are necessary to fully understand the role of the H⁺-K⁺ATPases in renal physiology.