Kraemer, Bernhard K. and Bergler, Tobias and Stoelcker, Benjamin and Waldegger, Siegfried (2008) Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. NATURE CLINICAL PRACTICE NEPHROLOGY, 4 (1). pp. 38-46. ISSN 1745-8323
Full text not available from this repository. (Request a copy)Abstract
Rodent ClC-K1 and ClC-K2, and their respective human orthologs ClCKA and ClCKB, are chloride channels specific to the kidney (and inner ear); Barttin is their functionally important subunit. ClC-K1 is predominantly localized to the thin ascending limb of the loop of Henle. ClC-K2 is expressed more broadly in the distal nephron; expression levels are highest along the thick ascending limb of the loop of Henle and distal convoluted tubule. Expression of ClC-K1 is upregulated by dehydration and downregulated by the diuretic furosemide, whereas expression of ClC-K2 is upregulated by furosemide and downregulated by high salt levels. ClCKA is important for maintenance of the corticomedullary osmotic gradient and the kidney's capacity to concentrate urine. If its ortholog, ClC-K1, is nonfunctional in mice, renal diabetes insipidus develops. ClCKB is a key determinant of tubular reabsorption of chloride and electrolytes along the distal tubule. A severe salt-losing tubulopathy (Bartter syndrome type III) develops if ClCKB is nonfunctional, whereas a common genetic variant of the CLCNKB gene that leads to increased activity of ClCKB results in salt-dependent hypertension. Disruption of the gene encoding Barttin, BSND, results in a 'double knockout' of the functions of both ClCKA and ClCKB, manifesting as Bartter syndrome type IV with sensorineural deafness and an especially severe salt-losing phenotype.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DISTAL-CONVOLUTED TUBULE; ZINC-FINGER REPRESSOR; CLC-K2 MESSENGER-RNA; THIN ASCENDING LIMB; GENE PROMOTER; RAT-KIDNEY; SENSORINEURAL DEAFNESS; SURFACE EXPRESSION; MOUSE KIDNEY; MICE LACKING; Bartter syndrome; Barttin; chloride channel; diabetes insipidus |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Abteilung für Nephrologie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 11 Dec 2020 10:45 |
| Last Modified: | 11 Dec 2020 10:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31726 |
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