Disease relevance of Clcnk1

• Localization and induction by dehydration of ClC-K chloride channels in the rat kidney [1].

High impact information on Clcnk1

• The localization and the functional characteristics described here indicate that ClC-K1 is responsible for the transepithelial chloride transport in tAL [2].
• Localization and functional characterization of rat kidney-specific chloride channel, ClC-K1 [2].
• Immunoelectron microscopy confirmed that the staining of ClC-K1 in tAL was observed in the region of both apical and basolateral plasma membranes [2].
• These results suggest that ClC-K2L and -K2S are chloride channels in the thick ascending limb and collecting ducts and may be important routes for transcellular chloride transport like ClC-K1 [3].
• We conclude that the descending thin limbs shift from expressing AQP1 to expressing ClC-K1 some distance before the point where they turn and begin to ascend [4].

Biological context of Clcnk1

• In the past few years the pivotal role of kidney Cl(-)channels (ClC-K) channels in maintaining salt and water homeostasis in the kidney has been established [5].
• Our findings imply that during furosemide treatment selective down-regulation of ClC-K1 and barttin mRNAs in thin limb plays a role in maintaining salt and water homeostasis [5].
• Functional analysis of BSND-associated point mutations revealed impaired ClC-K activation by barttin [6].

Anatomical context of Clcnk1

• To investigate the physiological role of a kidney-specific chloride channel (ClC-K1), we sought to determine its exact localization by immunohistochemistry and its functional regulation using Xenopus oocyte expression system [2].
• mRNA encoding 'ClC-K1, a kidney Cl(-)- channel' is expressed in marginal cells of the stria vascularis of rat cochlea: its possible contribution to Cl(-) currents [7].
• Thus these results demonstrate that rat kidney ClC-K channels are predominantly located in the basolateral membranes from cells of the late segments of the renal tubule where most of chloride reabsorption takes place [1].

Associations of Clcnk1 with chemical compounds

• In furosemide-treated rats ClC-K1 mRNA decreased to half in the inner medulla [5].

Regulatory relationships of Clcnk1

• Under furosemide treatment barttin mRNA was regulated in parallel with ClC-K1 mRNA [5].

Other interactions of Clcnk1

• Localisation and regulation of ClC-K1 and barttin mRNA was analysed by RNase protection and in situ hybridisation [5].
• The 687-amino acid protein encoded by ClC-K2L is about 80% identical to rat ClC-K1 and about 40% identical to ClC-0, -1, and -2 [3].
• At each level sampled in the inner medulla, many more thin limbs were labeled by ClC-K1 than AQP1 [4].
• We have isolated protein from the gerbil kidney, stria vascularis and vestibular labyrinth and found by Western blot analysis a 60 kDa band, a 48 kDa band and 54 and 70 kDa bands, respectively, specifically labeled by ClC-K antibody [8].

Analytical, diagnostic and therapeutic context of Clcnk1

• Northern blot and immunohistochemistry showed that ClC-K1 and ClC-K2 are selectively expressed in the kidney, while ClC-3 distributes in a variety of organs such as brain, lung, and kidney [9].
• We performed in situ hybridization on rat kidney slices and RT-PCR analysis on microdissected nephron segments to prove co-expression of barttin, ClC-K1 and ClC-K2 along the distal nephron [6].
• Co-immunoprecipitation revealed a direct interaction of barttin with ClC-K [6].
• The antiserum specifically recognized a 70-kD protein in SDS-PAGE of membrane protein from rat inner medulla and an in vitro translated ClC-K1 protein [2].

References