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Gene Review

Clcn2  -  chloride channel, voltage-sensitive 2

Rattus norvegicus

Synonyms: Chloride channel protein 2, ClC-2
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Disease relevance of Clcn2

  • Analysis of these results revealed that the membrane-delimited boundaries of the N- and C-termini of ClC-2 and the position of several extramembrane loops determined by these methods are largely similar to those predicted on the basis of the prokaryotic protein [ecClC (Escherichia coli ClC)] structures [1].
  • In the present report, we examined the hypothesis that ClC-2 plays a role in regulatory volume decrease by expressing ClC-2 in Sf9 cells using the baculovirus system [2].
  • Disruption of ClC-2-encoding gene in mouse leads to retinal and testicular degeneration and mutations in CLC2 (gene encoding the ClC-2 channel) are associated with idiopathic generalized epilepsies [3].

High impact information on Clcn2


Biological context of Clcn2


Anatomical context of Clcn2

  • The ClC-2 epithelial cell chloride channel is a voltage-, tonicity- and pH-regulated member of the ClC super family [7].
  • Deletion of amino acids 16-61 in rat ClC-2 abolishes voltage and pH dependence in two-electrode voltage-clamp experiments in amphibian oocytes [11].
  • Exposure of either cell line to high-dose glutamine is sufficient to induce glycosylation of SP1 and to induce and maintain ClC-2 [8].
  • Antibodies against the COOH terminus of ClC-2 reacted with a protein between 90 and 100 kDa in liver plasma membranes [12].
  • Taken together, these results indicate that dBcAMP-treated cultured rat cortical astrocytes express a Cl- inward rectifier, which exhibits similar but not identical features compared with those of the cloned and heterologously expressed hyperpolarization-activated Cl- channel ClC-2 [13].

Associations of Clcn2 with chemical compounds

  • The maxi Cl- channel (p-VDAC) blocker Gd3+, the ClC-2 inhibitor Cd2+, and the MDR-1 blocker verapamil did not affect EAA release or VRAC currents [14].
  • Functional characterization of novel alternatively spliced ClC-2 chloride channel variants in the heart [6].
  • A high level of luminal ClC-2 protein expression is maintained by the SP1 transcription factor until SP1 and ClC-2 decline rapidly at birth [8].
  • Aldosterone studies suggest that ClC-2 expression in the kidney may be hormonally regulated [9].
  • These results suggest that ClC-2 may be involved in estrogen-induced Cl(-) transport in rat kidney [9].
  • We conclude that the cholesterol environment regulates ClC-2 activity, and we provide evidence that the increase in ClC-2 activity in response to acute oxidative or metabolic stress involves relocalization of this channel to DSM [15].

Regulatory relationships of Clcn2


Other interactions of Clcn2


Analytical, diagnostic and therapeutic context of Clcn2


  1. Evaluation of the membrane-spanning domain of ClC-2. Ramjeesingh, M., Li, C., She, Y.M., Bear, C.E. Biochem. J. (2006) [Pubmed]
  2. ClC-2 activation modulates regulatory volume decrease. Xiong, H., Li, C., Garami, E., Wang, Y., Ramjeesingh, M., Galley, K., Bear, C.E. J. Membr. Biol. (1999) [Pubmed]
  3. The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p. Flis, K., Hinzpeter, A., Edelman, A., Kurlandzka, A. Biochem. J. (2005) [Pubmed]
  4. 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]
  5. Molecular dissection of gating in the ClC-2 chloride channel. Jordt, S.E., Jentsch, T.J. EMBO J. (1997) [Pubmed]
  6. Functional characterization of novel alternatively spliced ClC-2 chloride channel variants in the heart. Britton, F.C., Wang, G.L., Huang, Z.M., Ye, L., Horowitz, B., Hume, J.R., Duan, D. J. Biol. Chem. (2005) [Pubmed]
  7. Alternative mRNA splice variants of the rat ClC-2 chloride channel gene are expressed in lung: genomic sequence and organization of ClC-2. Chu, S., Zeitlin, P.L. Nucleic Acids Res. (1997) [Pubmed]
  8. Regulation of the ClC-2 lung epithelial chloride channel by glycosylation of SP1. Vij, N., Zeitlin, P.L. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  9. Estrogen modulates ClC-2 chloride channel gene expression in rat kidney. Nascimento, D.S., Reis, C.U., Goldenberg, R.C., Ortiga-Carvalho, T.M., Pazos-Moura, C.C., Guggino, S.E., Guggino, W.B., Morales, M.M. Pflugers Arch. (2003) [Pubmed]
  10. Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression. Holmes, K.W., Hales, R., Chu, S., Maxwell, M.J., Mogayzel, P.J., Zeitlin, P.L. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  11. Effect of an N-terminus deletion on voltage-dependent gating of the ClC-2 chloride channel. Varela, D., Niemeyer, M.I., Cid, L.P., Sepúlveda, F.V. J. Physiol. (Lond.) (2002) [Pubmed]
  12. Contribution of a time-dependent and hyperpolarization-activated chloride conductance to currents of resting and hypotonically shocked rat hepatocytes. Lan, W.Z., Abbas, H., Lam, H.D., Lemay, A.M., Hill, C.E. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  13. Characterization of an inwardly rectifying chloride conductance expressed by cultured rat cortical astrocytes. Ferroni, S., Marchini, C., Nobile, M., Rapisarda, C. Glia (1997) [Pubmed]
  14. Pharmacological comparison of swelling-activated excitatory amino acid release and Cl- currents in cultured rat astrocytes. Abdullaev, I.F., Rudkouskaya, A., Schools, G.P., Kimelberg, H.K., Mongin, A.A. J. Physiol. (Lond.) (2006) [Pubmed]
  15. Membrane cholesterol content modulates ClC-2 gating and sensitivity to oxidative stress. Hinzpeter, A., Fritsch, J., Borot, F., Trudel, S., Vieu, D.L., Brouillard, F., Baudouin-Legros, M., Clain, J., Edelman, A., Ollero, M. J. Biol. Chem. (2007) [Pubmed]
  16. 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]
  17. Distribution of chloride channel-2-immunoreactive neuronal and astrocytic processes in the hippocampus. Sík, A., Smith, R.L., Freund, T.F. Neuroscience (2000) [Pubmed]
  18. Arginine vasopressin regulates CFTR and ClC-2 mRNA expression in rat kidney cortex and medulla. Morales, M.M., Nascimento, D.S., Capella, M.A., Lopes, A.G., Guggino, W.B. Pflugers Arch. (2001) [Pubmed]
  19. Mast cells express chloride channels of the ClC family. Kulka, M., Schwingshackl, A., Befus, A.D. Inflamm. Res. (2002) [Pubmed]
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