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

1 Research Service, North Florida/South Georgia Veterans Health System and ; 2 Division of Nephrology, Hypertension, and Transplantation, Department of Medicine and ; 3 Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida Submitted December 2, 2008 ; accepted in final form July 23, 2009 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 -subunit and a regulatory β-subunit. There are two catalytic subunits present in the kidney, the gastric or HK 1 isoform and the colonic or HK 2 isoform. 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 HK 1 and HK 2 knockout 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 HK 1 and HK 2 suggest 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 HK 1 and HK 2 and 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. adenosine 5'-triphosphatase; potassium Address for reprint requests and other correspondence: C. S. Wingo, University of Florida, JHMHC PO Box 100224, Gainesville, FL 32610-0224 (e-mail: cswingo{at}ufl.edu ).