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Chloride Transporting CLC Proteins1

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Biological Membrane Ion Channels

Part of the book series: Biological And Medical Physics Biomedical Engineering ((BIOMEDICAL))

Abstract

In the early 1980s, Chris Miller and colleagues described a curious “double-barreled” chloride channel from the electric organ of Torpedo fish reconstituted in planar lipid bilayers (Miller and White, 1980). Single-channel openings occurred in “bursts” separated by long closures. A single burst was characterized by the presence of two open conductance levels of equal size and the gating (i.e., openings and closings) during a burst could be almost perfectly described as a superposition of two identical and independent conductances that switched between open and closed states with voltage-dependent rates α and β (Hanke and Miller, 1983) (Fig. 8.1).

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References

  • Accardi, A., L. Ferrera, and M. Pusch. 2001. Drastic reduction of the slow gate of human muscle chloride channel (C1C-1) by mutation C277S. J. Physiol. 534:745–752.

    Google Scholar 

  • Accardi, A., L. Kolmakova-Partensky, C. Williams, and C. Miller. 2004. Ionic currents mediated by a prokaryotic homologue of CLC Cl− channels. J. Gen. Physiol. 123:109–119. Epub 2004 Jan 12.

    Google Scholar 

  • Accardi, A., and C. Miller. 2004. Secondary active transport mediated by a prokaryotic homologue of C1C C1− channels. Nature 427:803–807.

    ADS  Google Scholar 

  • Accardi, A., and M. Pusch. 2000. Fast and slow gating relaxations in the muscle chloride channel CLC-1. J. Gen. Physiol. 116:433–444.

    Google Scholar 

  • Accardi, A., and M. Pusch. 2003. Conformational changes in the pore of CLC-0. J. Gen. Physiol. 122:277–293.

    Google Scholar 

  • Adachi, S., S. Uchida, H. Ito, M. Hata, M. Hiroe, F. Marumo, and S. Sasaki. 1994. Two isoforms of a chloride channel predominantly expressed in thick ascending limb of Henle’s loop and collecting ducts of rat kidney. J. Biol. Chem. 269:17677–17683.

    Google Scholar 

  • Adrian, R.H., and S.H. Bryant. 1974. On the repetitive discharge inmyotonic muscle fibres. J. Physiol. 240:505–515.

    Google Scholar 

  • Ahmed, N., M. Ramjeesingh, S. Wong, A. Varga, E. Garami, and C.E. Bear. 2000. Chloride channel activity of C1C-2 is modified by the actin cytoskeleton. Biochem. J. 352:789–794.

    Google Scholar 

  • Arreola, J., T. Begenisich, and J.E. Melvin. 2002. Conformation-dependent regulation of inward rectifier chloride channel gating by extracellular protons. J. Physiol. 541:103–112.

    Google Scholar 

  • Babini, E., and M. Pusch. 2004. A two-holed story: Structural secrets about CLC proteins become unraveled? Physiology 19:293–299. DOI:10.1152/physiol.00019.2004.

    Google Scholar 

  • Barbier-Brygoo, H., M. Vinauger, J. Colcombet, G. Ephritikhine, J. Frachisse, and C. Maurel. 2000. Anion channels in higher plants: Functional characterization, molecular structure and physiological role. Biochim. Biophys. Acta 1465:199–218.

    Google Scholar 

  • Bauer, C.K., K. Steinmeyer, J.R. Schwarz, and T.J. Jentsch. 1991. Completely functional double-barreled chloride channel expressed from a single Torpedo cDNA. Proc. Natl. Acad. Sei. USA 88:11052–11056.

    ADS  Google Scholar 

  • Bennetts, B., G.Y. Rychkov, H.-L. Ng, C.J. Morton, D. Stapleton, M.W. Parker, and B.A. Cromer. 2005. Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle C1C-1 chloride channels. J. Biol. Chem. 280:32452–32458.

    Google Scholar 

  • Birkenhäger, R., E. Otto, M.J. Schurmann, M. Vollmer, E.M. Ruf, I. Maier-Lutz, F. Beekmann, A. Fekete, H. Omran, D. Feldmann, D.V Milford, N. Jeck, M. Konrad, D. Landau, N. V. Knoers, C. Antignac, R. Sudbrak, A. Kispert, and F. Hildebrandt. 2001. Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat. Genet. 29:310–314.

    Google Scholar 

  • Blaisdell, C.J., R.D. Edmonds, X.T. Wang, S. Guggino, and P.L. Zeitlin. 2000. pH-regulated chloride secretion in fetal lung epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 278:L1248–L1255.

    Google Scholar 

  • Bösl, M.R., V Stein, C. Hübner, A.A. Zdebik, S.E. Jordt, A.K. Mukhopadhyay, M.S. Davidoff, A.F. Holstein, and T.J. Jentsch. 2001. Male germ cells and photoreceptors, both dependent on close cell–cell interactions, degenerate upon C1C-2 Cl(−) channel disruption. EMBO J. 20:1289–1299.

    Google Scholar 

  • Bostick, D.L., and M.L. Berkowitz. 2004. Exterior site occupancy infers chlorideinduced proton gating in a prokaryotic homolog of the C1C chloride channel. Biophys. J. 87:1686–1696.

    ADS  Google Scholar 

  • Brandt, S., and T.J. Jentsch. 1995. C1C-6 and C1C-7 are two novel broadly expressed members of the CLC chloride channel family. FEBS Lett. 377:15–20.

    Google Scholar 

  • Bretag, A.H. 1987. Muscle chloride channels. Physiol. Rev. 67:618–724.

    Google Scholar 

  • Bryant, S.H., and A. Morales-Aguilera. 1971. Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J. Physiol. 219:367–383.

    Google Scholar 

  • Buyse, G., D. Trouet, T. Voets, L. Missiaen, G. Droogmans, B. Nilius, and J. Eggermont. 1998. Evidence for the intracellular location of chloride channel (ClC)-type proteins: Co-localization of ClC-6a and ClC-6c with the sarco/endoplasmic-reticulum Ca2+ pump SERCA2b. Biochem. J. 330:1015–1021.

    Google Scholar 

  • Buyse, G., T. Voets, J. Tytgat, C. De Greef, G. Droogmans, B. Nilius, and J. Eggermont. 1997. Expression of human pIC1n and C1C-6 in xenopus oocytes induces an identical endogenous chloride conductance. J. Biol. Chem. 272:3615–3621.

    Google Scholar 

  • Catalán, M., M.I. Niemeyer, L.P. Cid, and F.V Sepúlveda. 2004. Basolateral C1C-2 chloride channels in surface colon epithelium: Regulation by a direct effect of intracellular chloride. Gastroenterology 126:1104–1114.

    Google Scholar 

  • Charlet, B.N., R.S. Savkur, G. Singh, A.V Philips, E.A. Grice, and T.A. Cooper. 2002. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol. Cell 10:45–53.

    Google Scholar 

  • Chen, M.F., and T.Y. Chen. 2001. Different fast-gate regulation by external Cl(−) and H(+) of the muscle-type C1C chloride channels. J. Gen. Physiol. 118:23–32.

    Google Scholar 

  • Chen, T.Y., M.F. Chen, and C.W. Lin. 2003. Electrostatic control and chloride regulation of the fast gating of C1C-0 chloride channels. J. Gen. Physiol. 122:641–651.

    Google Scholar 

  • Chen, T.Y., and C. Miller. 1996. Nonequilibrium gating and voltage dependence of the C1C-0 C1− channel. J. Gen. Physiol. 108:237–250.

    Google Scholar 

  • Cleiren, E., O. Benichou, E. Van Hul, J. Gram, J. Bollerslev, F.R. Singer, K. Beaverson, A. Aledo, M.P. Whyte, T. Yoneyama, M.C. de Vernejoul, and W. Van Hul. 2001. Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the C1CN7 chloride channel gene. Hum. Mol. Genet. 10:2861–2867.

    Google Scholar 

  • Cohen, J., and K. Schulten. 2004. Mechanism of anionic conduction across C1C. Biophys. J. 86:836–845.

    ADS  Google Scholar 

  • Conte-Camerino, D., M. Mambrini, A. DeLuca, D. Tricarico, S.H. Bryant, V. Tortorella, and G. Bettoni. 1988. Enantiomers of clofibric acid analogs have opposite actions on rat skeletal muscle chloride channels. Pflugers Arch. 413:105–107.

    Google Scholar 

  • Corry, B., M. O’Mara, and S.H. Chung. 2004. Conduction mechanisms of chloride ions in C1C-type channels. Biophys. J. 86:846–860.

    ADS  Google Scholar 

  • Dhani, S.U., and C.E. Bear. 2005. Role of intramolecular and intermolecular interactions in C1C channel and transporter function. Pflügers Arch. 16:16.

    Google Scholar 

  • Doyle, D.A., J. Morais Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. The structure of the potassium channel: Molecular basis of K+ conduction and selectivity. Science 280:69–77.

    ADS  Google Scholar 

  • Duffield, M., G. Rychkov, A. Bretag, and M. Roberts. 2003. Involvement of helices at the dimer Interface in C1C-1 common gating. J. Gen. Physiol. 121:149–161.

    Google Scholar 

  • Dutzler, R., E.B. Campbell, M. Cadene, B.T. Chait, and R. MacKinnon. 2002. X-ray structure of a C1C chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415:287–294.

    ADS  Google Scholar 

  • Dutzler, R., E.B. Campbell, and R. MacKinnon. 2003. Gating the selectivity filter in C1C chloride channels. Science 300:108–112.

    ADS  Google Scholar 

  • Embark, H.M., C. Bohmer, M. Palmada, J. Rajamanickam, A.W. Wyatt, S. Wallisch, G. Capasso, P. Waldegger, H.W. Seyberth, S. Waldegger, and F. Lang. 2004. Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-dependent kinases. Kidney Int. 66:1918–1925.

    Google Scholar 

  • Engh, A.M., and M. Maduke. 2005. Cysteine accessibility in C1C-0 supports conservation of the C1C intracellular vestibule. J. Gen. Physiol. 125:601–617.

    Google Scholar 

  • Estévez, R., T. Boettger, V Stein, R. Birkenhäger, E. Otto, F. Hildebrandt, and T.J. Jentsch. 2001. Barttin is a Cl− channel beta-subunit crucial for renal Cl− reabsorption and inner ear K+ secretion. Nature 414:558–561.

    ADS  Google Scholar 

  • Estévez, R., and T.J. Jentsch. 2002. CLC chloride channels: Correlating structure with function. Curr. Opin. Struct. Biol. 12:531–539.

    Google Scholar 

  • Estévez, R., M. Pusch, C. Ferrer-Costa, M. Orozco, and T.J. Jentsch. 2004. Functional and structural conservation of CBS domains from CLC channels. J. Physiol. 557:363–378.

    Google Scholar 

  • Estévez, R., B.C. Schroeder, A. Accardi, T.J. Jentsch, and M. Pusch. 2003. Conservation of chloride channel structure revealed by an inhibitor binding site in C1C-1. Neuron 38:47–59.

    Google Scholar 

  • Fahlke, C., R. Rüdel, N. Mitrovic, M. Zhou, and A.L. George Jr. 1995. An aspartic acid residue important for voltage-dependent gating of human muscle chloride channels. Neuron 15:463–472.

    Google Scholar 

  • Ferroni, S., C. Marchini, M. Nobile, and C. Rapisarda. 1997. Characterization of an inwardly rectifying chloride conductance expressed by cultured rat cortical astrocytes. Glia 21:217–227.

    Google Scholar 

  • Fong, P. 2004. CLC-K channels: If the drug fits, use it. EMBO Rep. 5:565–566.

    Google Scholar 

  • Fong, P., A. Rehfeldt, and T.J. Jentsch. 1998. Determinants of slow gating in C1C-0, the voltage-gated chloride channel of Torpedo marmorata. Am. J. Physiol. 274:C966–C973.

    Google Scholar 

  • Friedrich, T., T. Breiderhoff, and T.J. Jentsch. 1999. Mutational analysis demonstrates that C1C-4 and C1C-5 directly mediate plasma membrane currents. J. Biol. Chem. 274:896–902.

    Google Scholar 

  • Furukawa, T, T. Ogura, Y.J. Zheng, H. Tsuchiya, H. Nakaya, Y. Katayama, and N. Inagaki. 2002. Phosphorylation and functional regulation of C1C-2 chloride channels expressed in Xenopus oocytes by M cyclin-dependent protein kinase. J. Physiol. 540:883–893.

    Google Scholar 

  • Gentzsch, M., L. Cui, A. Mengos, X.B. Chang, J.H. Chen, and J.R. Riordan. 2003. The PDZ-binding chloride channel C1C-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. J. Biol. Chem. 278:6440–6449. Epub 2002 Dec 5.

    Google Scholar 

  • George, A.L., Jr., M.A. Crackower, J.A. Abdalla, A.J. Hudson, and G.C. Ebers. 1993. Molecular basis of Thomsen’s disease (autosomal dominant myotonia congenita). Nat. Genet. 3:305–310.

    Google Scholar 

  • Greger, R., and U. Windhorst. 1996. Comprehensive Human Physiology. Springer, Berlin.

    Google Scholar 

  • Gründer, S., A. Thiemann, M. Pusch, and T.J. Jentsch. 1992. Regions involved in the opening of ClC-2 chloride channel by voltage and cell volume. Nature 360:759–762.

    ADS  Google Scholar 

  • Günther, W., A. Luchow, F. Cluzeaud, A. Vandewalle, and T.J. Jentsch. 1998. C1C-5, the chloride channel mutated in Dent’s disease, colocalizes with the proton pump in endocytotically active kidney cells. Proc. Natl. Acad. Sci. USA 95:8075–8080.

    ADS  Google Scholar 

  • Günther, W., N. Piwon, and T.J. Jentsch. 2003. The C1C-5 chloride channel knockout mouse—an animal model for Dent’s disease. Pflügers Arch. 445:456–462. Epub 2002 Nov 29.

    Google Scholar 

  • Gyömörey, K., H. Yeger, C. Ackerley, E. Garami, and C.E. Bear. 2000. Expression of the chloride channel C1C-2 in the murine small intestine epithelium. Am. J. Physiol. Cell Physiol. 279:C1787–C1794.

    Google Scholar 

  • Hanke, W., and C. Miller. 1983. Single chloride channels from Torpedo electroplax. Activation by protons. J. Gen. Physiol. 82:25–45.

    Google Scholar 

  • Hara-Chikuma, M., Y. Wang, S.E. Guggino, W.B. Guggino, and A.S. Verkman.2005. Impaired acidification in early endosomes of C1C-5 deficient proximal tubule. Biochem. Biophys. Res. Commun. 329:941–946.

    Google Scholar 

  • Haug, K., M. Warnstedt, A.K. Alekov, T. Sander, A. Ramirez, B. Poser, S. Maljevic, S. Hebeisen, C. Kubisch, J. Rebstock, S. Horvath, K. Hallmann, J.S. Dullinger, B. Rau, F. Haverkamp, S. Beyenburg, H. Schulz, D. Janz, B. Giese, G. Muller-Newen, P. Propping, C.E. Elger, C. Fahlke, H. Lerche, and A. Heils. 2003. Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nat. Genet. 33:527–532.

    Google Scholar 

  • Hebeisen, S., A. Biela, B. Giese, G. Müller-Newen, P. Hidalgo, and C. Fahlke. 2004. The role of the carboxyl terminus in C1C chloride channel function. J. Biol. Chem. 279:13140–13147. Epub 2004 Jan 12.

    Google Scholar 

  • Hebeisen, S., H. Heidtmann, D. Cosmelli, C. Gonzalez, B. Poser, R. Latorre, O. Alvarez, and C. Fahlke. 2003. Anion permeation in human C1C-4 channels. Biophys. J. 84:2306–2318.

    Google Scholar 

  • Hechenberger, M., B. Schwappach, W.N. Fischer, W.B. Frommer, T.J. Jentsch, and K. Steinmeyer. 1996. A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruption. J. Biol. Chem. 271:33632–33638.

    Google Scholar 

  • Hille, B. 2001. Ion Channels of Excitable Membranes. Sinauer, Sunderland, MA.

    Google Scholar 

  • Hinzpeter, A., J. Lipecka, F. Brouillard, M. Baudouin-Legros, M. Dadlez, A. Edelman, and J. Fritsch. 2005. Association between Hsp90nand the C1C-2 chloride channel upregulates channel function. Am. J. Physiol. Cell Physiol. 00209.2005.

    Google Scholar 

  • Hori, K., Y. Takahashi, N. Horikawa, T. Furukawa, K. Tsukada, N. Takeguchi, and H. Sakai. 2004. Is the C1C-2 chloride channel involved in the C1-secretory mechanism of gastric parietal cells? FEES Lett. 575:105–108.

    Google Scholar 

  • Hryciw, D.H., J. Ekberg, A. Lee, I.L. Lensink, S. Kumar, W.B. Guggino, D.I. Cook, C.A. Pollock, and P. Poronnik. 2004. Nedd4-2 functionally interacts with C1C-5: Involvement in constitutive albumin endocytosis in proximal tubule cells. J. Biol. Chem. 279:54996–55007. Epub 2004 Oct 15.

    Google Scholar 

  • Hryciw, D.H., G.Y. Rychkov, B.P. Hughes, and A.H. Bretag. 1998. Relevance of the D13 region to the function of the skeletal muscle chloride channel, C1C-1. J. Biol. Chem. 273:4304–4307.

    Google Scholar 

  • Hryciw, D.H., Y. Wang, O. Devuyst, C.A. Pollock, P. Poronnik, and W.B. Guggino. 2003. Cofilin interacts with C1C-5 and regulates albumin uptake in proximal tubule cell lines. J. Biol. Chem. 278:40169–40176. Epub 2003 Aug 6.

    Google Scholar 

  • Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: Visual molecular dynamics. J. Mol. Graph. 14:33–38.

    Google Scholar 

  • Jentsch, T.J., M. Poet, J.C. Fuhrmann, and A.A. Zdebik. 2005. Physiological functions of CLC C1 channels gleaned from human genetic disease and mouse models. Ann. Rev. Physiol. 67:779–807.

    Google Scholar 

  • Jentsch, T.J., V. Stein, F. Weinreich, and A.A. Zdebik. 2002. Molecular structure and physiological function of chloride channels. Physiol. Rev. 82:503–568.

    Google Scholar 

  • Jentsch, T.J., K. Steinmeyer, and G. Schwarz. 1990. Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes. Nature 348:510–514.

    ADS  Google Scholar 

  • Jordt, S.E., and T.J. Jentsch. 1997. Molecular dissection of gating in the C1C-2 chloride channel. EMBO J. 16:1582–1592.

    Google Scholar 

  • Karsdal, M.A., K. Henriksen, M.G. Sorensen, J. Gram, S. Schaller, M.H. Dziegiel, A.M. Heegaard, P. Christophersen, T.J. Martin, C. Christiansen, and J. Bollerslev. 2005. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am. J. Pathol. 166:467–476.

    Google Scholar 

  • Kasper, D., R. Planells-Cases, J.C. Fuhrmann, O. Scheel, O. Zeitz, K. Ruether, A. Schmitt, M. Poet, R. Steinfeld, M. Schweizer, U. Kornak, and T.J. Jentsch. 2005. Loss of the chloride channel C1C-7 leads to lysosomal storage disease and neurodegeneration. EMBO J. 24:1079–1091. Epub 2005 Feb 10.

    Google Scholar 

  • Kieferle, S., P. Fong, M. Bens, A. Vandewalle, and T.J. Jentsch. 1994. Two highly homologous members of the C1C chloride channel family in both rat and human kidney. Proc. Natl. Acad. Sci. USA 91:6943–6947.

    ADS  Google Scholar 

  • Koch, M.C., K. Steinmeyer, C. Lorenz, K. Ricker, F. Wolf, M. Otto, B. Zoll, F. Lehmann-Horn, K.H. Grzeschik, and T.J. Jentsch. 1992. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 257:797–800.

    ADS  Google Scholar 

  • Kornak, U., D. Kasper, M.R. Bösl, E. Kaiser, M. Schweizer, A. Schulz, W. Friedrich, G. Delling, and T.J. Jentsch. 2001. Loss of the C1C-7 chloride channel leads to osteopetrosis in mice and man. Cell 104:205–215.

    Google Scholar 

  • Kung, C., and P. Blount. 2004. Channels in microbes: So many holes to fill. Mol. Microbiol. 53:373–380.

    Google Scholar 

  • Li, X., K. Shimada, L.A. Showalter, and S.A. Weinman. 2000. Biophysical properties of C1C-3 differentiate it from swelling-activated chloride channels in Chinese hamster ovary-K1 cells. J. Biol. Chem. 275:35994–35998.

    Google Scholar 

  • Li, X., T. Wang, Z. Zhao, and S.A. Weinman. 2002. The C1C-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells. Am. J. Physiol. Cell Physiol. 282:C1483–C1491.

    Google Scholar 

  • Liantonio, A., A. Accardi, G. Carbonara, G. Fracchiolla, F. Loiodice, P. Tortorella, S. Traverse, P. Guida, S. Pierno, A. De Luca, D.C. Camerino, and M. Pusch. 2002. Molecular requisites for drug binding to muscle CLC-1 and renal CLC-K channel revealed by the use of phenoxy-alkyl derivatives of 2-(p-chlorophenoxy)propionic acid. Mol. Pharmacol. 62:265–271.

    Google Scholar 

  • Liantonio, A., M. Pusch, A. Picollo, P. Guida, A. De Luca, S. Pierno, G. Fracchiolla, F. Loiodice, P. Tortorella, and D. Conte Camerino. 2004. Investigations of pharmacologic properties of the renal CLC-K1 chloride channel co-expressed with barttin by the use of 2-(p-Chlorophenoxy)propionic acid derivatives and other structurally unrelated chloride channels blockers. J. Am. Soc. Nephrol. 15:13–20.

    Google Scholar 

  • Lin, C.W., and T.Y. Chen. 2003. Probing the pore of C1C-0 by substituted cysteine accessibility method using methane thiosulfonate reagents. J. Gen. Physiol. 122:147–159.

    Google Scholar 

  • Lin, Y.W., C.W. Lin, and T.Y. Chen. 1999. Elimination of the slow gating of C1C-0 chloride channel by a point mutation. J. Gen. Physiol. 114:1–12.

    ADS  Google Scholar 

  • Lipecka, J., M. Bali, A. Thomas, P. Fanen, A. Edelman, and J. Fritsch. 2002. Distribution of C1C-2 chloride channel in rat and human epithelial tissues. Am. J. Physiol. Cell Physiol. 282:C805–C816.

    Google Scholar 

  • Lloyd, S.E., S.H. Pearce, S.E. Fisher, K. Steinmeyer, B. Schwappach, S.J. Scheinman, B. Harding, A. Bolino, M. Devoto, P. Goodyer, S.P. Rigden, O. Wrong, T.J. Jentsch, I.W. Craig, and R.V. Thakker. 1996. A common molecular basis for three inherited kidney stone diseases. Nature 379:445–449.

    ADS  Google Scholar 

  • Lorenz, C., M. Pusch, and T.J. Jentsch. 1996. Heteromultimeric CLC chloride channels with novel properties. Proc. Natl. Acad. Sci. USA 93:13362–13366.

    ADS  Google Scholar 

  • Ludewig, U., T.J. Jentsch, and M. Pusch. 1997a. Analysis of a protein region involved in permeation and gating of the voltage-gated Torpedo chloride channel C1C-0. J. Physiol. 498:691–702.

    Google Scholar 

  • Ludewig, U., T.J. Jentsch, and M. Pusch. 1997b. Inward rectification in C1C-0 chloride channels caused by mutations in several protein regions. J. Gen. Physiol. 110:165–171.

    Google Scholar 

  • Ludewig, U., M. Pusch, and T.J. Jentsch. 1996. Two physically distinct pores in the dimeric C1C-0 chloride channel. Nature 383:340–343.

    ADS  Google Scholar 

  • Maduke, M., D.J. Pheasant, and C. Miller. 1999. High-level expression, functional reconstitution, and quaternary structure of a prokaryotic C1C-type chloride channel. J. Gen. Physiol. 114:713–722.

    Google Scholar 

  • Maduke, M., C. Williams, and C. Miller. 1998. Formation of CLC-0 chloride channels from separated transmembrane and cytoplasmic domains. Biochemistry. 37:1315–1321.

    Google Scholar 

  • Mankodi, A., M.P. Takahashi, H. Jiang, C.L. Beck, W.J. Bowers, R.T. Moxley, S.C. Cannon, and C.A. Thornton. 2002. Expanded CUG repeats trigger aberrant splicing of C1C-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol. Cell 10:35–44.

    Google Scholar 

  • Matsumura, Y., S. Uchida, Y. Kondo, H. Miyazaki, S.B. Ko, A. Hayama, T. Morimoto, W. Liu, M. Arisawa, S. Sasaki, and F. Marumo. 1999. Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel. Nat. Genet. 21:95–98.

    Google Scholar 

  • Matulef, K., and M. Maduke. 2005. Side-dependent inhibition of a prokaryotic C1C by DIDS. Biophys. J. 89:1721–1730.

    ADS  Google Scholar 

  • Middleton, R.E., D.J. Pheasant, and C. Miller. 1996. Homodimeric architecture of a ClC-type chloride ion channel. Nature 383:337–340.

    ADS  Google Scholar 

  • Miller, C. 1982. Open-state substructure of single chloride channels from Torpedo electroplax. Philos. Trans. R. Soc. Lond. B Biol. Sci. 299:401–411.

    ADS  Google Scholar 

  • Miller, C., and M.M. White. 1980. A voltage-dependent chloride conductance channel from Torpedo electroplax membrane. Ann. N.Y. Acad. Sci. 341:534–551.

    ADS  Google Scholar 

  • Miller, C., and M.M. White. 1984. Dimeric structure of single chloride channels from Torpedo electroplax. Proc. Natl. Acad. Sci. USA 81:2772–2775.

    ADS  Google Scholar 

  • Miloshevsky, G.V., and P.C. Jordan. 2004. Anion pathway and potential energy profiles along curvilinear bacterial C1C C1− pores: Electrostatic effects of charged residues. Biophys. J. 86:825–835.

    ADS  Google Scholar 

  • Mindell, J.A., and M. Maduke. 2001. C1C chloride channels. Genome Biol. 2:Reviews 3003. Epub 2001 Feb 7.

    Google Scholar 

  • Mindell, J.A., M. Maduke, C. Miller, and N. Grigorieff. 2001. Projection structure of a ClC-type chloride channel at 6.5 A resolution. Nature 409:219–223.

    ADS  Google Scholar 

  • Mohammad-Panah, R., R. Harrison, S. Dhani, C. Ackerley, L.J. Huan, Y. Wang, and C.E. Bear. 2003. The chloride channel C1C-4 contributes to endosomal acidification and trafficking. J. Biol. Chem. 278:29267–29277.

    Google Scholar 

  • Muth, T.R., and M.J. Caplan. 2003. Transport protein trafficking in polarized cells. Ann. Rev. Cell Dev. Biol. 19:333–366.

    Google Scholar 

  • Nehrke, K., J. Arreola, H.V. Nguyen, J. Pilato, L. Richardson, G. Okunade, R. Baggs, G.E. Shull, and J.E. Melvin. 2002. Loss of hyperpolarization-activated C1(−) current in salivary acinar cells from Clcn2 knockout mice. J. Biol. Chem. 277:23604–23611. Epub 2002 Apr 25.

    Google Scholar 

  • Niemeyer, M.I., L.P. Cid, L. Zúñiga, M. Catalán, and F.V. Sepúlveda. 2003. A conserved pore-lining glutamate as a voltage- and chloride-dependent gate in the C1C-2 chloride channel. J. Physiol. 553:873–879. Epub 2003 Nov 14.

    Google Scholar 

  • Niemeyer, M.I., Y.R. Yusef, I. Cornejo, C.A. Flores, F.V. Sepúlveda, and L.P. Cid. 2004. Functional evaluation of human C1C-2 chloride channel mutations associated with idiopathic generalized epilepsies. Physiol. Genomics 13:13.

    Google Scholar 

  • Peña-Münzenmayer, G., M. Catalán, I. Cornejo, C.D. Figueroa, J.E. Melvin, M.I. Niemeyer, L.P. Cid, and F.V. Sepúlveda. 2005. Basolateral localization of native C1C-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif. J. Cell. Sci. 118:4243–4252.

    Google Scholar 

  • Picollo, A., A. Liantonio, M.P. Didonna, L. Elia, D.C. Camerino, and M. Pusch. 2004. Molecular determinants of differential pore blocking of kidney CLC-K chloride channels. EMBO Rep. 5:584–589. Epub 2004 May 28.

    Google Scholar 

  • Picollo, A., and M. Pusch. 2005. Chloride/proton antiporter activity of mammalian CLC proteins C1C-4 and C1C-5. Nature 436:420–423.

    ADS  Google Scholar 

  • Piwon, N., W. Günther, M. Schwake, M.R. Bösl, and T.J. Jentsch. 2000. C1C-5 Cl−-channel disruption impairs endocytosis in a mouse model for Dent’s disease. Nature 408:369–373.

    ADS  Google Scholar 

  • Ponting, C.P. 1997. CBS domains in ClC chloride channels implicated in myotonia and nephrolithiasis (kidney stones). J. Mol. Med. 75:160–163.

    Google Scholar 

  • Pusch, M. 2002. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum. Mutat. 19:423–434.

    Google Scholar 

  • Pusch, M. 2004. Structural insights into chloride and proton-mediated gating of CLC chloride channels. Biochemistry 43:1135–1144.

    Google Scholar 

  • Pusch, M., A. Accardi, A. Liantonio, L. Ferrera, A. De Luca, D.C. Camerino, and F. Conti. 2001. Mechanism of block of single protopores of the Torpedo chloride channel C1C-0 by 2-(p-chlorophenoxy)butyric acid (CPB). J. Gen. Physiol. 118:45–62.

    Google Scholar 

  • Pusch, M., A. Accardi, A. Liantonio, P. Guida, S. Traverso, D.C. Camerino, and F. Conti. 2002. Mechanisms of block of muscle type CLC chloride channels (Review). Mol. Membr. Biol. 19:285–292.

    Google Scholar 

  • Pusch, M., and T.J. Jentsch. 2005. Unique structure and function of chloride transporting CLC proteins. IEEE Trans. Nanobiosci. 4:49–57.

    Google Scholar 

  • Pusch, M., S.E. Jordt, V. Stein, and T.J. Jentsch. 1999. Chloride dependence of hyperpolarization-activated chloride channel gates. J. Physiol. 515:341–353.

    Google Scholar 

  • Pusch, M., A. Liantonio, L. Bertorello, A. Accardi, A. De Luca, S. Pierno, V. Tortorella, and D.C. Camerino. 2000. Pharmacological characterization of chloride channels belonging to the C1C family by the use of chiral clofibric acid derivatives. Mol. Pharmacol. 58:498–507.

    Google Scholar 

  • Pusch, M., U. Ludewig, and T.J. Jentsch. 1997. Temperature dependence of fast and slow gating relaxations of C1C-0 chloride channels. J. Gen. Physiol. 109:105–116.

    Google Scholar 

  • Pusch, M., U. Ludewig, A. Rehfeldt, and T.J. Jentsch. 1995a. Gating of the voltage-dependent chloride channel ClC-0 by the permeant anion. Nature 373:527–531.

    ADS  Google Scholar 

  • Pusch, M., K. Steinmeyer, and T.J. Jentsch. 1994. Low single channel conductance of the major skeletal muscle chloride channel, C1C-1. Biophys. J. 66:149–152.

    Google Scholar 

  • Pusch, M., K. Steinmeyer, M.C. Koch, and T.J. Jentsch. 1995b. Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the ClC-1 chloride channel. Neuron 15:1455–1463.

    Google Scholar 

  • Richard, E.A., and C. Miller. 1990. Steady-state coupling of ion-channel conformations to a transmembrane ion gradient. Science 247:1208–1210.

    ADS  Google Scholar 

  • Riordan, J.R., J.M. Rommens, B. Kerem, N. Alon, R. Rozmahel, Z. Grzelczak, J. Zielenski, S. Lok, N. Plavsic, J.L. Chou, M.L. Drumm, M.C. Iannuzzi, F.S. Collins, and L.-C. Tsui. 1989. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245:1066–1073.

    ADS  Google Scholar 

  • Rutledge, E., J. Denton, and K. Strange. 2002. Cell cycle- and swelling-induced activation of a Caenorhabditis elegans C1C channel is mediated by CeGLC-7alpha/beta phosphatases. J. Cell. Biol. 158:435–444. Epub 2002 Aug 5.

    Google Scholar 

  • Rychkov, G., M. Pusch, M. Roberts, and A. Bretag. 2001. Interaction of hydrophobic anions with the rat skeletal muscle chloride channel C1C-1: Effects on permeation and gating. J. Physiol 530:379–393.

    Google Scholar 

  • Rychkov, G.Y., M. Pusch, D.S. Astill, M.L. Roberts, T.J. Jentsch, and A.H. Bretag. 1996. Concentration and pH dependence of skeletal muscle chloride channel C1C-1. J. Physiol 497:423–435.

    Google Scholar 

  • Rychkov, G.Y., M. Pusch, M.L. Roberts, T.J. Jentsch, and A.H. Bretag. 1998. Permeation and block of the skeletal muscle chloride channel, C1C-1, by foreign anions. J. Gen. Physiol. 111:653–665.

    Google Scholar 

  • Saviane, C., F. Conti, and M. Pusch. 1999. The muscle chloride channel C1C-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. J. Gen. Physiol. 113:457–468.

    Google Scholar 

  • Sayle, R.A., and E.J. Milner-White. 1995. RASMOL: Biomolecular graphics for all. Trends Biochem. Sci. 20:374–376.

    Google Scholar 

  • Schaller, S., K. Henriksen, C. Sveigaard, A.M. Heegaard, N. Helix, M. Stahlhut, M.C. Ovejero, J.V. Johansen, H. Solberg, T.L. Andersen, D. Hougaard, M. Berryman, C.B. Shiodt, B.H. Sorensen, J. Lichtenberg, P. Christophersen, N.T. Foged, J.M. Delaisse, M.T. Engsig, and M.A. Karsdal. 2004. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation. J. Bone Miner. Res. 19:1144–1153.

    Google Scholar 

  • Scheel, O., A.A. Zdebik, S. Lourdel, and T.J. Jentsch. 2005. Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436:424–427.

    ADS  Google Scholar 

  • Schlingmann, K.P., M. Konrad, N. Jeck, P. Waldegger, S.C. Reinalter, M. Holder, H.W. Seyberth, and S. Waldegger. 2004. Salt wasting and deafness resulting from mutations in two chloride channels. N. Engl. J. Med. 350:1314–1319.

    Google Scholar 

  • Schriever, A.M., T. Friedrich, M. Pusch, and T.J. Jentsch. 1999. CLC chloride channels in Caenorhabditis elegans. J. Biol. Chem. 274:34238–34244.

    Google Scholar 

  • Schwappach, B., S. Stobrawa, M. Hechenberger, K. Steinmeyer, and T.J. Jentsch. 1998. Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Geflp. J. Biol. Chem. 273:15110–15118.

    Google Scholar 

  • Schwiebert, E.M., L.P. Cid-Soto, D. Stafford, M. Carter, C.J. Blaisdell, P.L. Zeitlin, W.B. Guggino, and G.R. Cutting. 1998. Analysis of C1C-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells. Proc. Natl. Acad. Sci. USA 95:3879–3884.

    ADS  Google Scholar 

  • Scott, J.W., S.A. Hawley, K.A. Green, M. Anis, G. Stewart, G.A. Scullion, D.G. Norman, and D.G. Hardie. 2004. CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J. Clin. Invest. 113:274–284.

    Google Scholar 

  • Sik, A., R.L. Smith, and T.F. Freund. 2000. Distribution of chloride channel-2-immunoreactive neuronal and astrocytic processes in the hippocampus. Neuroscience 101:51–65.

    Google Scholar 

  • Simon, D.B., R.S. Bindra, T.A. Mansfield, C. Nelson-Williams, E. Mendonca, R. Stone, S. Schurman, A. Nayir, H. Alpay, A. Bakkaloglu, J. Rodriguez-Soriano, J.M. Morales, S.A. Sanjad, C.M. Taylor, D. Pilz, A. Brem, H. Trachtman, W. Griswold, G.A. Richard, E. John, and R.P. Lifton. 1997. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat. Genet. 17:171–178.

    Google Scholar 

  • Simon, D.B., F.E. Karet, J.M. Hamdan, A.D. Pietro, S.A. Sanjad, and R.P. Lifton. 1996a. Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2CI cotransporter NKCC2. Nat. Genet. 13:183–188.

    Google Scholar 

  • Simon, D.B., F.E. Karet, J. Rodriguez-Soriano, J.H. Hamdan, A. DiPietro, H. Trachtman, S.A. Sanjad, and R.P. Lifton. 1996b. Genetic heterogeneity of Barter’s syndrome revealed by mutations in the K+ channel, ROMK. Nat. Genet. 14:152–156.

    Google Scholar 

  • Staley, K., R. Smith, J. Schaack, C. Wilcox, and T.J. Jentsch. 1996. Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel. Neuron 17:543–551.

    Google Scholar 

  • Steinmeyer, K., R. Klocke, C. Ortland, M. Gronemeier, H. Jockusch, S. Gründer, and T.J. Jentsch. 1991a. Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature 354:304–308.

    ADS  Google Scholar 

  • Steinmeyer, K., C. Lorenz, M. Pusch, M.C. Koch, and T.J. Jentsch. 1994. Multimeric structure of C1C-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J. 13:737–743.

    Google Scholar 

  • Steinmeyer, K., C. Ortland, and T.J. Jentsch. 1991b. Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature 354:301–304.

    ADS  Google Scholar 

  • Steinmeyer, K., B. Schwappach, M. Bens, A. Vandewalle, and T.J. Jentsch. 1995. Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease. J. Biol. Chem. 270:31172–31177.

    Google Scholar 

  • Stobrawa, S.M., T. Breiderhoff, S. Takamori, D. Engel, M. Schweizer, A.A. Zdebik, M.R. Bösl, K. Ruether, H. Jahn, A. Draguhn, R. Jahn, and T.J. Jentsch. 2001. Disruption of C1C-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29:185–196.

    Google Scholar 

  • Strange, K. 2003. From genes to integrative physiology: Ion channel and transporter biology in Caenorhabditis elegans. Physiol. Rev. 83:377–415.

    Google Scholar 

  • Thiemann, A., S. Gründer, M. Pusch, and T.J. Jentsch. 1992. A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356:57–60.

    ADS  Google Scholar 

  • Traverso, S., L. Elia, and M. Pusch. 2003. Gating competence of constitutively open CLC-0 mutants revealed by the interaction with a small organic Inhibitor. J. Gen. Physiol. 122:295–306.

    Google Scholar 

  • Uchida, S., S. Sasaki, T. Furukawa, M. Hiraoka, T. Imai, Y. Hirata, and F. Marumo. 1993. Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla. J. Biol. Chem. 268:3821–3824.

    Google Scholar 

  • Uchida, S., S. Sasaki, K. Nitta, K. Uchida, S. Horita, H. Nihei, and F. Marumo. 1995. Localization and functional characterization of rat kidney-specific chloride channel, C1C-K1. J. Clin. Invest. 95:104–113.

    Google Scholar 

  • Vandewalle, A., F. Cluzeaud, M. Bens, S. Kieferle, K. Steinmeyer, and T.J. Jentsch. 1997. Localization and induction by dehydration of C1C-K chloride channels in the rat kidney. Am. J. Physiol. 272:F678–F688.

    Google Scholar 

  • Vanoye, C.G., and A.L. George Jr. 2002. Functional characterization of recombinant human C1C-4 chloride channels in cultured mammalian cells. J. Physiol. 539:373–383.

    Google Scholar 

  • Waldegger, S., and T.J. Jentsch. 2000. Functional and structural analysis of C1C-K chloride channels involved in renal disease. J. Biol. Chem. 275:24527–24533.

    Google Scholar 

  • Wang, S.S., O. Devuyst, P.J. Courtoy, X.T. Wang, H. Wang, Y. Wang, R.V. Thakker, S. Guggino, and W.B. Guggino. 2000. Mice lacking renal chloride channel, CLC-5, are a model for Dent’s disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. Hum. Mol. Genet. 9:2937–2945.

    Google Scholar 

  • Weinreich, F., and T.J. Jentsch. 2001. Pores formed by single subunits in mixed dimers of different CLC chloride channels. J. Biol. Chem. 276:2347–2353.

    Google Scholar 

  • Yin, J., Z. Kuang, U. Mahankali, and T.L. Beck. 2004. Ion transit pathways and gating in C1C chloride channels. Proteins 57:414–421.

    Google Scholar 

  • Zdebik, A.A., J.E. Cuffe, M. Bertog, C. Korbmacher, and T.J. Jentsch. 2004. Additional disruption of the C1C-2 Cl− channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models. J. Biol. Chem. 279:22276–22283.

    Google Scholar 

  • Zheng, Y.J., T. Furukawa, T. Ogura, K. Tajimi, and N. Inagaki. 2002. M phase-specific expression and phosphorylation-dependent ubiquitination of the C1C-2 channel. J. Biol Chem. 277:32268–32273. Epub 2002 Jun 24.

    Google Scholar 

  • Zúñiga, L., M.I. Niemeyer, D. Varela, M. Catalán, L.P. Cid, and F.V. SepZúlveda. 2004. The voltage-dependent C1C-2 chloride channel has a dual gating mechanism. J. Physiol 555:671–682. Epub 2004 Jan 14.

    Google Scholar 

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  1. Istituto di Biofisica CNR, Via de Marini 6, Genova, I-16149, Italy

    Michael Pusch

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  1. Res. School of Biological Sciences, Australian National University, Canberra, ACT 0200, Australia

    Shin-Ho Chung

  2. Weill Medical College Dept. Physiology, Cornell University, 1300 York Avenue, New York, NY, 10021, USA

    Olaf S. Andersen

  3. Dept. of Elect. & Comp. Engi., University of British Columbia, MacLeod Bulding, Vancouver, BC, Canada

    Vikram Krishnamurthy

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Pusch, M. (2007). Chloride Transporting CLC Proteins1 . In: Chung, SH., Andersen, O.S., Krishnamurthy, V. (eds) Biological Membrane Ion Channels. Biological And Medical Physics Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/0-387-68919-2_8

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