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.