title: Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting.
abstract: BACKGROUND
  The epithelial calcium channel (ECaC) (TRPV5) and the Cl-/HCO3- exchanger pendrin (SLC26A4) are expressed on the apical membrane of tubular cells in the distal nephron and play essential roles in calcium re-absorption and bicarbonate secretion, respectively, in the kidney.
  
  
  METHODS
  A combination of functional and molecular biology techniques were employed to examine the role of pendrin deletion in calcium excretion.
  
  
  RESULTS
  Here, we demonstrate that deletion of pendrin causes acidic urine [urine pH 4.9 in knockout (KO) versus 5.9 in wild-type (WT) mice, P<0.03)] and downregulates the calcium-absorbing molecules ECaC and Na/Ca exchanger in the kidney, as shown by northern hybridization, immunoblot analysis and/or immunofluorescent labeling. These changes were associated with a ∼100% increase in 24-h urine calcium excretion in pendrin null mice. Subjecting the pendrin WT and KO mice to oral bicarbonate loading for 12 days increased the urine pH to ∼8 in both genotypes, normalized the expression of ECaC and Na/Ca exchanger and reduced the urine calcium excretion in pendrin-null mice to levels comparable to WT mice.
  
  
  CONCLUSIONS
  We suggest that pendrin dysfunction should be suspected and investigated in humans with an otherwise unexplained acidic urine and hypercalciuria.
authors.affiliation: Research Services, Veterans Administration Medical Center, Cincinnati, OH, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Barone
authors.forename: Hassane
authors.initials: H
authors.lastname: Amlal
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000042:Absorption; D000818:Animals; D027321:Anion Transport Proteins / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000652:urine*; D015220:Calcium Channels / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D000076988:Sulfate Transporters; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D001639:Bicarbonates; D015220:Calcium Channels; D027963:Chloride-Bicarbonate Antiporters; C494849:Slc26a4 protein, mouse; D019831:Sodium-Calcium Exchanger; D000076988:Sulfate Transporters; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002118:Calcium