Disease relevance of Clcnka

• After 24 hours of water deprivation, Clcnk1-/- mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight [1].
• These results indicate that the polyuria observed in Clcnk1-/- mice was water diuresis and not osmotic diuresis [2].
• To functionally express the promoter, the approximately 2.5-kb pair 5'-flanking region was ligated to a luciferase reporter gene and transfected into inner medullary (IM) cells, a stable ClC-K1-expressing cell line derived from the inner medulla of simian virus 40 transgenic mouse, and ClC-K1-nonexpressing cell lines [3].

High impact information on Clcnka

• After in vitro perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in Clcnk1-/- mice in contrast to Clcnk1+/+ and Clcnk1+/- mice [1].
• Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel [1].
• CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla [1].
• Further, the lower renal inner medullary interstitial NaCl concentration that occurs chronically in ClCK1(-/-) mice and acutely in normal mice given furosemide is associated with lower NTE mRNA and protein [4].
• Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Krüppel-like factor, a novel zinc finger repressor [5].

Biological context of Clcnka

• Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride channel [6].

Anatomical context of Clcnka

• Discontinuous axial expression of AQP1, UT-A2, and ClC-K1 along the straight portion of single thin limbs indicates that these nephrons possess a more heterogeneous structure than previously recognized [7].
• We therefore examined whether kidney-specific chloride channels (ClC-K1 and ClC-K2) and ClC-5 are also expressed in OHCs of rat cochlea, assuming that these channels might be the targets of oto-nephrotoxic drugs, by single-cell reverse transcription-polymerase chain reaction (RT-PCR) technique [8].
• mRNA expression of kidney-specific ClC-K1 chloride channel in single-cell reverse transcription-polymerase chain reaction analysis of outer hair cells of rat cochlea [8].
• Luciferase activity was 7-to 24-fold greater in IM cells than those in nonexpressing cell lines, suggesting that the approximately 2.5-kb fragment contained cis-acting regulatory elements for cell-specific expression of the ClC-K1 gene [3].

Associations of Clcnka with chemical compounds

• Furthermore, the accumulation of urea was also impaired in Clcnk1-/- mice, suggesting that the overall countercurrent system was impaired by a defect of its single component, chloride transport in the tAL [2].
• These results suggest that the novel purine-rich element may play a key role in the activity of the ClC-K1 gene promoter [3].

Other interactions of Clcnka

• Since immunohistochemical data indicates that ClC-K2, and perhaps ClC-K1, are present on the DCT basolateral membrane, we suggest that the channel detected in this study may belong to this subfamily of the ClC channel family [9].
• We concluded that NDI in Clcnk1-/- mice resulted from an impairment in the generation of inner medullary hypertonicity by a dysfunction of the countercurrent systems [2].
• The aldose reductase mRNA abundance in Clcnk1-/- mice was decreased, further evincing that inner medullary tonicity is decreased in Clcnk1-/- mice [2].
• The addition of 300 microg/ml protamine, a selective blocker of paracellular conductance, to the bath increased the V(d) values by 5.6 +/- 0.7 and 12.6 +/- 1.5 mV (P < 0.001) in CLC-K1(+/+) and CLC-K1(-/-) mice, respectively [10].

References