|
Originally published In Press as doi:10.1074/jbc.M001987200 on May 30, 2000
J. Biol. Chem., Vol. 275, Issue 32, 24527-24533, August 11, 2000
Functional and Structural Analysis of ClC-K Chloride Channels
Involved in Renal Disease*
Siegfried
Waldegger and
Thomas J.
Jentsch
From the Zentrum für Molekulare Neurobiologie, University of
Hamburg, Martinistr. 85, D-20246 Hamburg, Germany
ClC-K channels belong to the CLC family of
chloride channels and are predominantly expressed in the kidney.
Genetic evidence suggests their involvement in transepithelial
transport of chloride in distal nephron segments; ClC-K1 gene deletion
leads to nephrogenic diabetes insipidus in mice, and mutations of the
hClC-Kb gene cause Bartter's syndrome type III in humans. Expression
of rClC-K1 in Xenopus oocytes yielded voltage-independent
currents that were pH-sensitive, had a Br > NO3 = Cl > I conductance sequence, and were activated by
extracellular calcium. A glutamate for valine exchange at amino acid
position 166 induced strong voltage dependence and altered the
conductance sequence of ClC-K1. This demonstrates that rClC-K1 indeed
functions as an anion channel. By contrast, we did not detect currents
upon hClC-Kb expression in Xenopus oocytes. Using a
chimeric approach, we defined a protein domain that, when replaced by
that of rClC-K1, allowed the functional expression of a chimera
consisting predominantly of hClC-Kb. Its currents were linear and were
inhibited by extracellular acidification. Contrasting with rClC-K1,
they displayed a Cl > Br > I > NO3 conductance sequence and were
not augmented by extracellular calcium. Insertion of point mutations
associated with Bartter's syndrome type III destroyed channel
activity. We conclude that ClC-K proteins form constitutively open
chloride channels with distinct physiological characteristics.
*
This work was supported by grants from the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen Industrie (to
T. J. J.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: ZMNH, University of
Hamburg, Martinistr. 85, D-20246 Hamburg, Germany. Fax:
49-40-42803-4839; E-mail:
siegfried.waldegger@zmnh.uni-hamburg.de.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G. Frindt, A. Shah, J. Edvinsson, and L. G. Palmer
Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney
Am J Physiol Renal Physiol,
February 1, 2009;
296(2):
F347 - F354.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Zdebik, G. Zifarelli, E.-Y. Bergsdorf, P. Soliani, O. Scheel, T. J. Jentsch, and M. Pusch
Determinants of Anion-Proton Coupling in Mammalian Endosomal CLC Proteins
J. Biol. Chem.,
February 15, 2008;
283(7):
4219 - 4227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Jentsch
Chloride Transport in the Kidney: Lessons from Human Disease and Knockout Mice
J. Am. Soc. Nephrol.,
June 1, 2005;
16(6):
1549 - 1561.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. G. Lionetto, M. E. Giordano, F. De Nuccio, G. Nicolardi, E. K. Hoffmann, and T. Schettino
Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium
J. Exp. Biol.,
February 15, 2005;
208(4):
749 - 760.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Nissant, S. Lourdel, S. Baillet, M. Paulais, P. Marvao, J. Teulon, and M. Imbert-Teboul
Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp
Am J Physiol Renal Physiol,
December 1, 2004;
287(6):
F1233 - F1243.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Liantonio, M. Pusch, A. Picollo, P. Guida, A. De Luca, S. Pierno, G. Fracchiolla, F. Loiodice, P. Tortorella, and D. C. Camerino
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.,
January 1, 2004;
15(1):
13 - 20.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Auzanneau, V. Thoreau, A. Kitzis, and F. Becq
A Novel Voltage-dependent Chloride Current Activated by Extracellular Acidic pH in Cultured Rat Sertoli Cells
J. Biol. Chem.,
May 23, 2003;
278(21):
19230 - 19236.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Lourdel, M. Paulais, P. Marvao, A. Nissant, and J. Teulon
A Chloride Channel at the Basolateral Membrane of the Distal-convoluted Tubule: a Candidate ClC-K Channel
J. Gen. Physiol.,
March 31, 2003;
121(4):
287 - 300.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Liantonio, A. Accardi, G. Carbonara, G. Fracchiolla, F. Loiodice, P. Tortorella, S. Traverso, P. Guida, S. Pierno, A. De Luca, et al.
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.,
August 1, 2002;
62(2):
265 - 271.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Galvan, J. Rexach, V. Mariscal, and E. Fernandez
Nitrite transport to the chloroplast in Chlamydomonas reinhardtii: molecular evidence for a regulated process
J. Exp. Bot.,
April 15, 2002;
53(370):
845 - 853.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Jentsch, V. Stein, F. Weinreich, and A. A. Zdebik
Molecular Structure and Physiological Function of Chloride Channels
Physiol Rev,
April 1, 2002;
82(2):
503 - 568.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Vandewalle
Diversity within the CLC chloride channel family involved in inherited diseases: from plasma membranes to acidic organelles
Nephrol. Dial. Transplant.,
January 1, 2002;
17(1):
1 - 3.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. K. Wills and P. Fong
ClC Chloride Channels in Epithelia: Recent Progress and Remaining Puzzles
Physiology,
August 1, 2001;
16(4):
161 - 166.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Fahlke
Ion permeation and selectivity in ClC-type chloride channels
Am J Physiol Renal Physiol,
May 1, 2001;
280(5):
F748 - F757.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|