The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Clcn3  -  chloride channel, voltage-sensitive 3

Rattus norvegicus

Synonyms: Chloride channel protein 3, Chloride transporter ClC-3, ClC-3, H(+)/Cl(-) exchange transporter 3
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Clcn3

  • ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery [1].
  • In this study, we have shown that heterologous expression of ClC-3 in either Chinese hamster ovary (CHO-K1) or human hepatoma (Huh-7) cells results in the formation of large, acidic vesicular structures within cells [2].
  • This study is the first to demonstrate changes in mRNA levels of HCN2, HCN4, and ClC-3 in cardiac hypertrophy induced by abdominal aortic banding [3].
  • Treatment with the antioxidant, Trolox (2 mg/kg body weight), prevented the initial increase in ClC-3 and Na(+)/Ca(2+) exchanger proteins [4].
  • The up-regulation of ClC-3 and Na(+)/Ca(2+) exchanger proteins during the early stages of diabetes and its prevention by antioxidants suggests that the proteins regulating ion transport may have a pathophysiological role in the development of diabetic cataracts [4].

High impact information on Clcn3

  • A detailed analysis revealed that ClC-3 was expressed by type B intercalated cells, whereas ClC-5 was expressed by type A intercalated cells [5].
  • Biophysical properties of ClC-3 differentiate it from swelling-activated chloride channels in Chinese hamster ovary-K1 cells [6].
  • These data suggest that ClC-3 cannot be responsible for the swelling-activated chloride channel under all circumstances [6].
  • However, recent studies have shown that native ClC-3 in hepatocytes is primarily intracellular [6].
  • Whereas ClC-5 is localized intracellularly, ClC-3 has been reported to be a swelling-activated plasma membrane channel [6].

Biological context of Clcn3

  • However, the amino acid sequence was weakly homologous to those of other ClC Cl- channels except for ClC-3, which we recently identified as a Ca2+-sensitive ORCC [7].
  • Cl- channels have been implicated in essential cellular functions including volume regulation, progression of cell cycle, cell proliferation and contraction, but the physiological functions of the ClC-3 channel are controversial [1].
  • In conclusion, upregulation of ClC-3 in rat hypertensive lung and heart is a novel observation [1].
  • Adenovirus-mediated delivery and overexpression of ClC-3 in canine PASMCs improved cell viability against increasing concentrations of hydrogen peroxide (H2O2, range 50-250 microM) [1].
  • 6. Polymerase chain reaction followed by DNA sequence analysis indicated the presence of mRNA homologous to the ClC-3 chloride channel in pancreatic tissue from 5-day-old rats [8].

Anatomical context of Clcn3


Associations of Clcn3 with chemical compounds

  • Changes in mRNA levels of HCN2, HCN4, and ClC-3 were alleviated by both candesartan and amlodipine, and these levels of the treated groups were not different from those in the sham control group [3].
  • These results suggest that ClC-2, ClC-3 and ICln either participate in taurine transport themselves or upregulate an endogenous oocyte osmolyte channel [10].

Physical interactions of Clcn3

  • 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 [9].

Other interactions of Clcn3

  • Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated [11].
  • 1. The expression of ClC-3 was examined in rat lacrimal gland and submandibular salivary gland cells using RT-PCR and Western analysis [12].
  • The levels of ClC-2 in both atria and ventricles were significantly less than those measured for ClC-3 (n = 3; P < 0.05) [13].
  • RT-PCR revealed the presence of transcripts of ClC-1, ClC-2 and ClC-3, which were verified by DNA sequencing [14].
  • This study investigates changes in the messenger RNA (mRNA) expression levels of HCN2 and HCN4 encoding rat If channels; ClC-3, a candidate gene for swelling-activated Cl- channel, and pICln, a regulatory subunit of Cl- channels in rat hypertrophied heart induced by banding the abdominal aorta [3].

Analytical, diagnostic and therapeutic context of Clcn3


  1. ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery. Dai, Y.P., Bongalon, S., Hatton, W.J., Hume, J.R., Yamboliev, I.A. Br. J. Pharmacol. (2005) [Pubmed]
  2. The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells. Li, X., Wang, T., Zhao, Z., Weinman, S.A. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  3. Ion channel remodeling in cardiac hypertrophy is prevented by blood pressure reduction without affecting heart weight increase in rats with abdominal aortic banding. Hiramatsu, M., Furukawa, T., Sawanobori, T., Hiraoka, M. J. Cardiovasc. Pharmacol. (2002) [Pubmed]
  4. Oxidative stress-induced up-regulation of the chloride channel and Na+/Ca2+ exchanger during cataractogenesis in diabetic rats. Ramana, K.V., Chandra, D., Wills, N.K., Bhatnagar, A., Srivastava, S.K. J. Diabetes Complicat. (2004) [Pubmed]
  5. 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. Obermüller, N., Gretz, N., Kriz, W., Reilly, R.F., Witzgall, R. J. Clin. Invest. (1998) [Pubmed]
  6. Biophysical properties of ClC-3 differentiate it from swelling-activated chloride channels in Chinese hamster ovary-K1 cells. Li, X., Shimada, K., Showalter, L.A., Weinman, S.A. J. Biol. Chem. (2000) [Pubmed]
  7. Identification of a new outwardly rectifying Cl- channel that belongs to a subfamily of the ClC Cl- channels. Sakamoto, H., Kawasaki, M., Uchida, S., Sasaki, S., Marumo, F. J. Biol. Chem. (1996) [Pubmed]
  8. Characterization of cell volume-sensitive chloride currents in freshly prepared and cultured pancreatic acinar cells from early postnatal rats. Schmid, A., Blum, R., Krause, E. J. Physiol. (Lond.) (1998) [Pubmed]
  9. Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM. Isnard-Bagnis, C., Da Silva, N., Beaulieu, V., Yu, A.S., Brown, D., Breton, S. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  10. Swelling-induced taurine release without chloride channel activity in Xenopus laevis oocytes expressing anion channels and transporters. Stegen, C., Matskevich, I., Wagner, C.A., Paulmichl, M., Lang, F., Bröer, S. Biochim. Biophys. Acta (2000) [Pubmed]
  11. ClC family in the kidney. Sasaki, S., Uchida, S., Kawasaki, M., Adachi, S., Marumo, F. Jpn. J. Physiol. (1994) [Pubmed]
  12. Expression of volume-sensitive Cl(-) channels and ClC-3 in acinar cells isolated from the rat lacrimal gland and submandibular salivary gland. Majid, A., Brown, P.D., Best, L., Park, K. J. Physiol. (Lond.) (2001) [Pubmed]
  13. Molecular distribution of volume-regulated chloride channels (ClC-2 and ClC-3) in cardiac tissues. Britton, F.C., Hatton, W.J., Rossow, C.F., Duan, D., Hume, J.R., Horowitz, B. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  14. Single-cell RT-PCR demonstrates expression of voltage-dependent chloride channels (ClC-1, ClC-2 and ClC-3) in outer hair cells of rat cochlea. Kawasaki, E., Hattori, N., Miyamoto, E., Yamashita, T., Inagaki, C. Brain Res. (1999) [Pubmed]
  15. Expression and canalicular localization of two isoforms of the ClC-3 chloride channel from rat hepatocytes. Shimada, K., Li, X., Xu, G., Nowak, D.E., Showalter, L.A., Weinman, S.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  16. The intracellular region of ClC-3 chloride channel is in a partially folded state and a monomer. Li, S.J., Kawazaki, M., Ogasahara, K., Nakagawa, A. J. Biochem. (2006) [Pubmed]
WikiGenes - Universities