title: Proximal tubular NHEs: sodium, protons and calcium?
abstract: Na⁺/H⁺ exchange activity in the apical membrane of the proximal tubule is fundamental to the reabsorption of Na⁺ and water from the filtrate. The role of this exchange process in bicarbonate reclamation and, consequently, the maintenance of acid-base homeostasis has been appreciated for at least half a century and remains a pillar of renal tubular physiology. More recently, apical Na⁺/H⁺ exchange, mediated by Na⁺/H⁺ exchanger isoform 3 (NHE3), has been implicated in proximal tubular reabsorption of Ca²⁺ and Ca²⁺ homeostasis in general. Overexpression of NHE3 increased paracellular Ca²⁺ flux in a proximal tubular cell model. Consistent with this observation, mice with genetic deletion of Nhe3 have a noticable renal Ca²⁺ leak. These mice also display decreased intestinal Ca²⁺ uptake and osteopenia. This review highlights the traditional roles of proximal tubular Na⁺/H⁺ exchange and summarizes recent novel findings implicating the predominant isoform, NHE3, in Ca²⁺ homeostasis.
authors.affiliation: Department of Pediatrics, Edmonton Clinic Health Academy, 11405-87 Ave., University of Alberta, Edmonton, AB, Canada T6G 2R7. todd2@ualberta.ca
authors.forename: R Todd
authors.initials: RT
authors.lastname: Alexander
authors.forename: Henrik
authors.initials: H
authors.lastname: Dimke
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cordat
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011522:Protons; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D010281:Parathyroid Hormone; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D014867:Water; D006859:Hydrogen; D012964:Sodium; D002118:Calcium
keywords: calcium; paracellular; parathyroid hormone; proximal tubule; sodium-hydrogen exchanger isoform 3