title: Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia.
abstract: The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is an ammonia-specific transporter heavily expressed in the kidney and is necessary for the normal increase in ammonia excretion in response to metabolic acidosis. Hypokalemia is a common clinical condition in which there is increased renal ammonia excretion despite the absence of metabolic acidosis. The purpose of this study was to examine Rhbg's role in this response through the use of mice with intercalated cell-specific Rhbg deletion (IC-Rhbg-KO). Hypokalemia induced by feeding a K(+)-free diet increased urinary ammonia excretion significantly. In mice with intact Rhbg expression, hypokalemia increased Rhbg protein expression in intercalated cells in the cortical collecting duct (CCD) and in the outer medullary collecting duct (OMCD). Deletion of Rhbg from intercalated cells inhibited hypokalemia-induced changes in urinary total ammonia excretion significantly and completely prevented hypokalemia-induced increases in urinary ammonia concentration, but did not alter urinary pH. We conclude that hypokalemia increases Rhbg expression in intercalated cells in the cortex and outer medulla and that intercalated cell Rhbg expression is necessary for the normal increase in renal ammonia excretion in response to hypokalemia.
authors.affiliation: Division of Nephrology, Hypertension, and Transplantation, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Bishop
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: Mary E
authors.initials: ME
authors.lastname: Handlogten
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Han
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.forename: I David
authors.initials: ID
authors.lastname: Weiner
mesh_terms: D000641:Ammonia / Q000378:metabolism* / Q000652:urine; D000818:Animals; D017353:Gene Deletion; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007008:Hypokalemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017419:Potassium, Dietary / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D026901:Membrane Transport Proteins; D017419:Potassium, Dietary; C486033:RhBG protein, mouse; D000641:Ammonia