title: The swelling-activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells.
abstract: The mammalian genome encodes at least nine different members of the ClC family of chloride channels. So far only two of them could be localized on a cellular level in the kidney. We now report on the precise intrarenal localization of the mRNAs coding for the chloride channels ClC-2, ClC-3 and ClC-5. Expression of ClC-2 mRNA, encoding a swelling-activated chloride channel, could be demonstrated in the S3 segment of the proximal tubule. The chloride channel ClC-3 mRNA and ClC-5 mRNA, coding for a chloride channel mutated in kidney stone disease, were both expressed in intercalated cells of the connecting tubule and collecting duct. Whereas ClC-3 mRNA expression was most prominent in the cortex of rat kidneys, ClC-5 mRNA was expressed from the cortex through the upper portion of the inner medulla. A detailed analysis revealed that ClC-3 was expressed by type B intercalated cells, whereas ClC-5 was expressed by type A intercalated cells. These findings have important implications for the pathogenesis of hereditary kidney stone disease caused by mutations in the CLCN5 gene.
authors.affiliation: Medical Research Center, Klinikum Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Obermüller
authors.forename: N
authors.initials: N
authors.lastname: Gretz
authors.forename: W
authors.initials: W
authors.lastname: Kriz
authors.forename: R F
authors.initials: RF
authors.lastname: Reilly
authors.forename: R
authors.initials: R
authors.lastname: Witzgall
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000096:biosynthesis* / Q000235:genetics*; D004195:Disease Models, Animal; D004847:Epithelial Cells; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007669:Kidney Calculi / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; C115376:ClC-3 channel; D012333:RNA, Messenger