title: Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney.
abstract: CLC-K2, a kidney-specific member of the CLC chloride channel family, is thought to play an important role in the transepithelial Cl(-) transport in the kidney. This consensus was first reached shortly after it was demonstrated that the mutations of the human CLCNKB gene resulted in Bartter's syndrome type III. To clarify the pathogenesis, the exact intrarenal and cellular localization of CLC-K2 by immunohistochemistry of the Clcnk1-/- mouse kidney were investigated by use of an anti-CLC-K antibody that recognized both CLC-K1 and CLC-K2. CLC-K2 is expressed in the thick ascending limb of Henle's loop and distal tubules, where it is localized to the basolateral membranes. The localization of CLC-K2 to these nephron segments strongly implies that CLC-K2 confers the basolateral chloride conductance in the thick ascending limb of Henle's loop and distal tubules, where Cl(-) is taken up by the bumetanide-sensitive Na-K-2Cl cotransporter or the thiazide-sensitive Na-Cl cotransporter at the apical membranes. CLC-K2 expression was also shown to extend into the connecting tubule in the basolateral membrane. CLC-K2 was found in basolateral membranes of the type A intercalated cells residing along the collecting duct. This localization strongly suggests that CLC-K2 confers the basolateral conductance in the type A intercalated cells where Cl(-) is taken up by the anion exchanger in exchange for HCO(3)(-) at the basolateral membranes. These aspects of CLC-K2 localization suggest that CLC-K2 is important in Cl(-) transport in the distal nephron segments.
authors: Department of Pediatrics, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors: Katsuki
authors: K
authors: Kobayashi
authors: Second Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors: Shinichi
authors: S
authors: Uchida
authors: Department of Pediatrics, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors: Shuki
authors: S
authors: Mizutani
authors: Second Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors: Sei
authors: S
authors: Sasaki
authors: Second Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors: Fumiaki
authors: F
authors: Marumo
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D012016:Reference Values; D014018:Tissue Distribution
chemical_list: D027321:Anion Transport Proteins; D018118:Chloride Channels; C486573:Clcnkb protein, mouse; D008565:Membrane Proteins