title: NHA2 is expressed in distal nephron and regulated by dietary sodium.
abstract: Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na+(Li+)/H+antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H+-coupled Na+(Li+) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2. In murine kidney sections, NHA2 localized apically to distal convoluted (both DCT1 and 2) and connecting tubules, partially overlapping in distribution with V-ATPase, AQP2, and NCC1 transporters. Mice fed a diet high in sodium chloride showed elevated transcripts and expression of NHA2 protein. We propose a model in which NHA2 plays a dual role in salt reabsorption or secretion, depending on the coupling ion (sodium or protons). The identified novel regulation of Na+/H+antiporter in the kidney suggests new roles in salt homeostasis and disease.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA.|Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Road, Dearborn, MI, 48128, USA.
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Kondapalli
authors.affiliation: Division of Nephrology, Department of Pediatrics, University of Alberta, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Todd Alexander
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pluznick
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA. rrao@jhmi.edu.
authors.forename: Rajini
authors.identifier: http://orcid.org/0000-0002-1833-5971
authors.initials: R
authors.lastname: Rao
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D051399:Aquaporin 2 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity; D005786:Gene Expression Regulation; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009399:Nephrons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D049992:Sodium Chloride Symporters / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D012982:Sodium, Dietary / Q000008:administration & dosage* / Q000009:adverse effects; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D017920:Antiporters; C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D015415:Biomarkers; C526786:NHA2 protein, mouse; D012333:RNA, Messenger; D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary; D012982:Sodium, Dietary; D025262:Vacuolar Proton-Translocating ATPases
keywords: Hypertension; NHEDC2; Na+/H+ antiport; Nephron; SLC; Sodium diet