title: The chloride channel/transporter Slc26a9 regulates the systemic arterial pressure and renal chloride excretion.
abstract: Apical chloride secretory pathways in the kidney medullary collecting duct are thought to play an important role in the modulation of final urine composition and regulation of systemic vascular volume and/or blood pressure. However, the molecular identity of these molecules has largely remained unknown. Here, we demonstrate that Slc26a9, an electrogenic chloride channel/transporter, is localized on the apical membrane of principal cells in the kidney medullary collecting duct and mediates chloride secretion. Mice with the genetic deletion of Slc26a9 show significant reduction in renal chloride excretion when fed a diet high in salt or subjected to water deprivation. Arterial pressure measurements indicated that Slc26a9 knockout (Slc26a9(-/-)) mice are hypertensive under baseline conditions and increase their blood pressure further within 48 h of switching to a high-salt diet. These results suggest that Slc26a9 plays an important role in renal chloride/fluid excretion and arterial pressure regulation. We propose that impaired SLC26A9 activity in humans may interfere with the excretion of excess salt and result in hypertension.
authors.affiliation: Research Services, Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors.forename: Hassane
authors.initials: H
authors.lastname: Amlal
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Sharon
authors.initials: S
authors.lastname: Barone
authors.forename: Kamyar
authors.initials: K
authors.lastname: Zahedi
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000818:Animals; D017920:Antiporters / Q000172:deficiency / Q000235:genetics*; D062186:Arterial Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002414:Cations, Monovalent; D002712:Chlorides / Q000378:metabolism*; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D012964:Sodium / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism; D000076988:Sulfate Transporters; D014867:Water / Q000378:metabolism
chemical_list: D017920:Antiporters; D002414:Cations, Monovalent; D002712:Chlorides; C533708:Slc26a9 protein, mouse; D017673:Sodium Chloride, Dietary; D000076988:Sulfate Transporters; D014867:Water; D012964:Sodium