THE SWELLING-ACTIVATED CHLORIDE CHANNEL CIC-2, THE CHLORIDE CHANNEL CIC-3, AND CIC-5, A CHLORIDE CHANNEL MUTATED IN KIDNEY-STONE DISEASE, ARE EXPRESSED IN DISTINCT SUBPOPULATIONS OF RENAL EPITHELIAL-CELLS

The mammalian genome encodes at least nine different members of the Cl C family of chloride channels. So far only two of them could be locali zed on a cellular level in the kidney. We now report on the precise in trarenal localization of the mRNAs coding for the chloride channels Cl C-2, ClC-3 and ClC-5. Expression of ClC-2 mRNA, encoding a swelling-ac tivated chloride channel, could be demonstrated in the S3 segment of t he proximal tubule. The chloride channel ClC-3 mRNA and ClC-5 mRNA, co ding for a chloride channel mutated in kidney stone disease, were both expressed in intercalated cells of the connecting tubule and collecti ng duct, Whereas ClC-3 mRNA expression was most prominent in the corte x 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 e xpressed by type A intercalated cells. These findings have important i mplications for the pathogenesis of hereditary kidney stone disease ca used by mutations in the CLCN5 gene.