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 CIC 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 CIC-2, CIC-3 and CIC-5. Expression of CIC-2 mRNA, encoding a swelling-activated chloride channel, could be demonstrated in the S3 segment of the proximal tubule. The chloride channel CIC-3 mRNA and CIC-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 CIC-3 mRNA expression was most prominent in the cortex of rat kidneys, CIC-5 mRNA was expressed from the cortex through the upper portion of the inner medulla. A detailed analysis revealed that CIC-3 was expressed by type B intercalated cells, whereas CIC-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.