Disease relevance of Clcn5

• 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 [1].
• ClC-5 is the Cl- channel that is mutated in Dent's disease, an X-chromosome-linked disease characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones [2].
• Corresponding to the increase in ClC-5 expression, the albuminuria in SHR improved to the control level [3].
• These results implicate the ClC-5 Cl(-) channel reduction in the development of albuminuria in the early stage of essential hypertension [3].

High impact information on Clcn5

• A detailed analysis revealed that ClC-3 was expressed by type B intercalated cells, whereas ClC-5 was expressed by type A intercalated cells [1].
• We now report on the precise intrarenal localization of the mRNAs coding for the chloride channels ClC-2, ClC-3 and ClC-5 [1].
• The molecular structure and functional properties of ClC-5 will provide an important insight into ORCCs and the pathogenesis of Dent's disease [4].
• To characterize the functional properties of ClC-5 by whole cell patch-clamp technique, we established the stably transfected CHO-K1 cell line using intranuclear microinjection technique [4].
• Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption [5].

Biological context of Clcn5

• To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1alpha,25(OH)(2) vitamin D(3) with and without thyroparathyroidectomy [5].
• Tissue distribution and subcellular localization of the ClC-5 chloride channel in rat intestinal cells [2].
• These findings suggest that ClC-5 might be involved in the endocytosis and/or the H+ secretion in the proximal tubule cells and the cortical collecting duct type A intercalated cells in mouse kidney [6].

Anatomical context of Clcn5

• Whereas ClC-5 is localized intracellularly, ClC-3 has been reported to be a swelling-activated plasma membrane channel [7].
• ClC-5 might facilitate endosome trafficking in the epididymis, as has been proposed in the kidney [8].
• Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM [8].
• A subfractionation of vesicles obtained by differential centrifugation showed that ClC-5 is associated with the vacuolar 70-kDa H+-ATPase and the small GTPases rab4 and rab5a, two markers of early endosomes [2].
• Thus these results indicate that ClC-5 is present in the small intestine and colon of rats and suggest that it plays a role in the endocytotic pathways of intestinal cells [2].

Associations of Clcn5 with chemical compounds

• In addition, using immunocytochemistry, we find that ClC-5 is predominantly expressed along the luminal surface of the airway epithelium, suggesting that ClC-5 may participate in lung chloride secretion [9].
• The ClC-5 protein level was partially restored by short term administration of perindopril, an inhibitor of angiotensin-converting enzyme [3].

Physical interactions of Clcn5

• These findings are consistent with a potential role for ClC-3 in transepithelial chloride transport by principal cells and for ClC-5 in the acidification of H(+)-ATPase-containing vesicles in narrow and clear cells [8].

Other interactions of Clcn5

• Single-cell RT-PCR revealed the presence of transcripts of ClC-K1 in OHCs which was verified by DNA sequencing, while ClC-K2 and ClC-5 were not detected [10].

Analytical, diagnostic and therapeutic context of Clcn5

• Northern blot analysis of rat tissues showed that ClC-5 mRNA was predominantly expressed in the kidney and colon [4].
• Confocal microscopy showed that ClC-5 partially colocalizes with the H(+)-ATPase in the subapical pole of clear cells [8].
• Western blot analyses revealed the presence of the 83-kDa ClC-5 protein in these tissues [2].
• Indirect immunofluorescence studies showed that ClC-5 was mainly concentrated in the cytoplasm above the nuclei of enterocytes and colon cells [2].
• Immunoblotting demonstrated an 85-kDa band of ClC-5 in the kidney and ClC-5 transfected cells [6].

References