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The swelling-activated chloride channel CIC-2, the chloride channel CIC-3, and CIC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells
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Gunther W, Luchow A, Cluzeaud F, Vandewalle A, Jentsch TJ: CIC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells. Proc Natl Acad Sci USA 1998, 95:8075-8080. Dent's disease is caused by mutations in CIC-5 and is characterized by hypercalciuria and low-molecular-weight proteinuria. Although we still have no clue to explain how alterations on CIC-5 channel might result in hypercalciuria, the present work casts light on the pathophysiology of the proteinuria. The expression of CIC-5 in renal proximal tubule endocytic vesicles suggest that this channel might be needed to provide an electrical shunt required for vesicular acidification and therefore protein endocytosis. The functional properties of the CIC-5 channel have been studied in a more recent work and discuss in relation to its vesicular location (see [78•]).
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79
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Mutational analysis demonstrates that CIC-4 and CIC-5 directly mediate plasma membrane currents
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-, strong outward rectification and are sensitive to extracellular pH. Similar to other CIC channels, mutations introduced at the ends of transmembrane domain D2 alters ion selectivity in CIC-5 and mutations at the end of D3 alter the gating and the conductance sequence in both channels.
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Mutations in the chloride channel gene CLCNKB cause Bartter's syndrome type III
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Simon, D.B.1
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82
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Matsumura Y, Uchida S, Kondo Y, Miyazaki H, Ko SBH, Hayama A, Morimoto T, Liu W, Arisawa M, Sasaki S, Marumo F: Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel. Nat Genet 1999, 21:95-98. Nephrogenic diabetes insipidus (NDI) is characterized by the kidneys' inability to respond to antidiuretic hormone and therefore an excess loss of water occurs. Although previous studies have shown the importance of other genes in relation with this disease, the present work provides compelling evidence on the role of CIC-K1 in chloride handling by the Henle's loop and the pathophysiology of the disease.
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Nat Genet
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Matsumura, Y.1
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