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

J Clin Invest. 1998 Feb 1;101(3):635-42. doi: 10.1172/JCI1496.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chloride Channels / biosynthesis*
  • Chloride Channels / genetics*
  • Disease Models, Animal
  • Epithelial Cells
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Calculi / metabolism*
  • Kidney Calculi / pathology
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Male
  • Mutation*
  • Osmolar Concentration
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • CLC-5 chloride channel
  • Chloride Channels
  • ClC-3 channel
  • RNA, Messenger