A. Vandewalle, F. Cluzeaud, M. Bens, S. Kieferle, K. Steinmeyer et al., Localization and induction by dehydration of ClC-K chloride channels in the rat kidney, Am J Physiol, vol.272, pp.678-688, 1997.

R. Estevez, T. Boettger, V. Stein, R. Birkenhager, E. Otto et al., Barttin is a Cl -channel beta-subunit crucial for renal Cl -reabsorption and inner ear K + secretion, Nature, vol.414, pp.558-561, 2001.

K. Kobayashi, S. Uchida, S. Mizutani, S. Sasaki, and F. Marumo, Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney, J Am Soc Nephrol, vol.12, pp.1327-1334, 2001.

C. Fahlke and M. Fischer, Physiology and pathophysiology of ClC-K/barttin channels, Front Physiol, vol.1, p.155, 2010.

D. B. Simon, R. S. Bindra, T. A. Mansfield, C. Nelson-williams, E. Mendonca et al., Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III, Nat Genet, vol.17, pp.171-178, 1997.

M. Konrad, M. Vollmer, H. H. Lemmink, L. P. Van-den-heuvel, N. Jeck et al., Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome, J Am Soc Nephrol, vol.11, pp.1449-1459, 2000.

R. Birkenhager, E. Otto, M. J. Schurmann, M. Vollmer, E. M. Ruf et al., Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure, Nat Genet, vol.29, pp.310-314, 2001.

K. P. Schlingmann, M. Konrad, N. Jeck, P. Waldegger, S. C. Reinalter et al., Salt wasting and deafness resulting from mutations in two chloride channels, N Engl J Med, vol.350, pp.1314-1319, 2004.

Y. Matsumura, S. Uchida, Y. Kondo, H. Miyazaki, S. B. Ko et al., Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel, Nat Genet, vol.21, pp.95-98, 1999.

S. Adachi, S. Uchida, H. Ito, M. Hata, M. Hiroe et al., 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, vol.269, pp.17677-17683, 1994.

S. Kieferle, P. Fong, M. Bens, A. Vandewalle, and T. J. Jentsch, Two highly homologous members of the ClC chloride channel family in both rat and human kidney, Proc Natl Acad Sci U S A, vol.91, pp.6943-6947, 1994.

S. Waldegger, N. Jeck, P. Barth, M. Peters, H. Vitzthum et al., Barttin increases surface expression and changes current properties of ClC-K channels, Pflugers Arch, vol.444, pp.411-418, 2002.

U. Scholl, S. Hebeisen, A. G. Janssen, G. Muller-newen, A. Alekov et al., Barttin modulates trafficking and function of ClC-K channels, Proc Natl Acad Sci U S A, vol.103, pp.11411-11416, 2006.

M. Fischer, A. G. Janssen, and C. Fahlke, Barttin activates ClC-K channel function by modulating gating, J Am Soc Nephrol, vol.21, pp.1281-1289, 2010.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral renal medullary membranes: III. Determinants of single-channel activity, J Membr Biol, vol.118, pp.269-278, 1990.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral renal medullary membrane vesicles: IV. Analogous channel activation by Cl -or cAMP-dependent protein kinase, J Membr Biol, vol.122, pp.89-95, 1991.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral TAL membranes. XIV. Kinetic properties of a basolateral MTAL Cl -channel, Kidney Int, vol.55, pp.1444-1449, 1999.

R. Sauve, S. Cai, L. Garneau, H. Klein, and L. Parent, pH and external Ca 2+ regulation of a small conductance Cl -channel in kidney distal tubule, Biochim Biophys Acta, vol.1509, pp.73-85, 2000.

M. Paulais and J. , Teulon, cAMP-activated chloride channel in the basolateral membrane of the thick ascending limb of the mouse kidney, J Membr Biol, vol.113, pp.253-260, 1990.

R. Guinamard, A. Chraibi, and J. Teulon, A small-conductance Cl -channel in the mouse thick ascending limb that is activated by ATP and protein kinase A, J Physiol, vol.485, pp.97-112, 1995.

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, vol.121, pp.287-300, 2003.
URL : https://hal.archives-ouvertes.fr/hal-02453227

A. Nissant, S. Lourdel, S. Baillet, M. Paulais, P. Marvao et al., Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp, Am J Physiol Renal Physiol, vol.287, pp.1233-1243, 2004.

A. Nissant, M. Paulais, S. Lachheb, S. Lourdel, and J. Teulon, Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney, Am J Physiol Renal Physiol, vol.290, pp.1421-1429, 2006.

J. Teulon, S. Lourdel, A. Nissant, M. Paulais, R. Guinamard et al., Imbert-Teboul, Exploration of the basolateral chloride channels in the renal tubule using the patch-clamp technique, Nephron Physiol, vol.99, pp.64-68, 2005.

S. Waldegger and T. J. Jentsch, Functional and structural analysis of ClC-K chloride channels involved in renal disease, J Biol Chem, vol.275, pp.24527-24533, 2000.

A. Diakov, K. Bera, M. Mokrushina, B. Krueger, and C. Korbmacher, Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels, J Physiol, vol.586, pp.4587-4608, 2008.

B. Krueger, S. Haerteis, L. Yang, A. Hartner, R. Rauh et al., Cholesterol depletion of the plasma membrane prevents activation of the epithelial sodium channel (ENaC) by SGK1, Cell Physiol Biochem, vol.24, pp.605-618, 2009.

N. Zerangue, B. Schwappach, Y. N. Jan, and L. Y. Jan, A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels, Neuron, vol.22, pp.537-548, 1999.

S. Uchida, S. Sasaki, T. Furukawa, M. Hiraoka, T. Imai et al., Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla, J Biol Chem, vol.269, p.19192, 1994.

S. Uchida, S. Sasaki, K. Nitta, K. Uchida, S. Horita et al., Localization and functional characterization of rat kidney-specific chloride channel, ClC-K1, J Clin Invest, vol.95, pp.104-113, 1995.

A. Liantonio, M. Pusch, A. Picollo, P. Guida, A. De-luca et al., 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, vol.15, pp.13-20, 2004.

L. Feng, E. B. Campbell, Y. Hsiung, and R. Mackinnon, Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle, Science, vol.330, pp.635-641, 2010.

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

R. Dutzler, E. B. Campbell, and R. Mackinnon, Gating the selectivity filter in ClC chloride channels, Science, vol.300, pp.108-112, 2003.

A. G. Janssen, U. Scholl, C. Domeyer, D. Nothmann, A. Leinenweber et al., Disease-causing dysfunctions of barttin in Bartter syndrome type IV, J Am Soc Nephrol, vol.20, pp.145-153, 2009.

G. Zifarelli, A. Liantonio, A. Gradogna, A. Picollo, G. Gramegna et al., Identification of sites responsible for the potentiating effect of niflumic acid on ClC-Ka kidney chloride channels, Br J Pharmacol, vol.160, pp.1652-1661, 2010.

A. Liantonio, A. Picollo, E. Babini, G. Carbonara, G. Fracchiolla et al., Activation and inhibition of kidney CLC-K chloride channels by fenamates, Mol Pharmacol, vol.69, pp.165-173, 2006.

T. Y. Chen, Structure and function of clc channels, Annu Rev Physiol, vol.67, pp.809-839, 2005.

G. Rickheit, H. Maier, N. Strenzke, C. E. Andreescu, C. I. De-zeeuw et al., Endocochlear potential depends on Cl -channels: mechanism underlying deafness in Bartter syndrome IV, Embo J, vol.27, pp.2907-2917, 2008.

S. Uchida and S. Sasaki, Function of chloride channels in the kidney, Annu Rev Physiol, vol.67, pp.759-78, 2005.

N. Akizuki, S. Uchida, S. Sasaki, and F. Marumo, Impaired solute accumulation in inner medulla of Clcnk1-/-mice kidney, Am J Physiol Renal Physiol, vol.280, pp.79-87, 2001.

, Single-channel activity in HEK293 cells reflects dimer gating of mClC-K1

, ClC channels, which function as dimer complexes, are endowed with two voltage-dependent gates, the protopore

, Since the ClC-K channels have a valine residue at position 166 rather than a glutamate, it may be anticipated that their voltage dependence is due to common gating. Accordingly, the experiments we performed in the cell-attached mode in HEK293 transfected cells showed that half openings and closings of mClC-K1 due to protopore gating were rarely detected in these recordings. As a consequence, the NP o values found in these experiments essentially reflect the activity of the common gate. Thus, the common gate of mClC-K1 channels is moderately activated by depolarization. It is noteworthy that the half-maximal activation voltage V 1/2 (~ -65 mV), which is close to the resting membrane potential in renal cells, suggests that this regulation might be physiologically relevant, Protopore gating requires the presence of a glutamate at equivalent position 166. Indeed, substituting glutamate for valine

, We also observed that mClC-K1 currents were greater in the presence of Barttin. However

, This segment absorbs 25% of filtered NaCl by the operation of a Na + -K + -2Cl -cotransporter at the apical membrane, and the presence of Na + -K + ATPase at the basolateral membrane. Cl -conductance is necessary for the basolateral step of Cl -absorption. ClC-K1 probably plays only a minor role

A. Vandewalle, F. Cluzeaud, M. Bens, S. Kieferle, K. Steinmeyer et al., Localization and induction by dehydration of ClC-K chloride channels in the rat kidney, Am J Physiol, vol.272, pp.678-688, 1997.

R. Estevez, T. Boettger, V. Stein, R. Birkenhager, E. Otto et al., Barttin is a Cl -channel beta-subunit crucial for renal Cl -reabsorption and inner ear K + secretion, Nature, vol.414, pp.558-561, 2001.

K. Kobayashi, S. Uchida, S. Mizutani, S. Sasaki, and F. Marumo, Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney, J Am Soc Nephrol, vol.12, pp.1327-1334, 2001.

C. Fahlke and M. Fischer, Physiology and pathophysiology of ClC-K/barttin channels, Front Physiol, vol.1, p.155, 2010.

D. B. Simon, R. S. Bindra, T. A. Mansfield, C. Nelson-williams, E. Mendonca et al., Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III, Nat Genet, vol.17, pp.171-178, 1997.

M. Konrad, M. Vollmer, H. H. Lemmink, L. P. Van-den-heuvel, N. Jeck et al., Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome, J Am Soc Nephrol, vol.11, pp.1449-1459, 2000.

R. Birkenhager, E. Otto, M. J. Schurmann, M. Vollmer, E. M. Ruf et al., Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure, Nat Genet, vol.29, pp.310-314, 2001.

K. P. Schlingmann, M. Konrad, N. Jeck, P. Waldegger, S. C. Reinalter et al., Salt wasting and deafness resulting from mutations in two chloride channels, N Engl J Med, vol.350, pp.1314-1319, 2004.

Y. Matsumura, S. Uchida, Y. Kondo, H. Miyazaki, S. B. Ko et al., Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel, Nat Genet, vol.21, pp.95-98, 1999.

S. Adachi, S. Uchida, H. Ito, M. Hata, M. Hiroe et al., 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, vol.269, pp.17677-17683, 1994.

S. Kieferle, P. Fong, M. Bens, A. Vandewalle, and T. J. Jentsch, Two highly homologous members of the ClC chloride channel family in both rat and human kidney, Proc Natl Acad Sci U S A, vol.91, pp.6943-6947, 1994.

S. Waldegger, N. Jeck, P. Barth, M. Peters, H. Vitzthum et al., Barttin increases surface expression and changes current properties of ClC-K channels, Pflugers Arch, vol.444, pp.411-418, 2002.

U. Scholl, S. Hebeisen, A. G. Janssen, G. Muller-newen, A. Alekov et al., Barttin modulates trafficking and function of ClC-K channels, Proc Natl Acad Sci U S A, vol.103, pp.11411-11416, 2006.

M. Fischer, A. G. Janssen, and C. Fahlke, Barttin activates ClC-K channel function by modulating gating, J Am Soc Nephrol, vol.21, pp.1281-1289, 2010.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral renal medullary membranes: III. Determinants of single-channel activity, J Membr Biol, vol.118, pp.269-278, 1990.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral renal medullary membrane vesicles: IV. Analogous channel activation by Cl -or cAMP-dependent protein kinase, J Membr Biol, vol.122, pp.89-95, 1991.

C. J. Winters, W. B. Reeves, and T. E. Andreoli, Cl-channels in basolateral TAL membranes. XIV. Kinetic properties of a basolateral MTAL Cl -channel, Kidney Int, vol.55, pp.1444-1449, 1999.

R. Sauve, S. Cai, L. Garneau, H. Klein, and L. Parent, pH and external Ca 2+ regulation of a small conductance Cl -channel in kidney distal tubule, Biochim Biophys Acta, vol.1509, pp.73-85, 2000.

M. Paulais and J. , Teulon, cAMP-activated chloride channel in the basolateral membrane of the thick ascending limb of the mouse kidney, J Membr Biol, vol.113, pp.253-260, 1990.

R. Guinamard, A. Chraibi, and J. Teulon, A small-conductance Cl -channel in the mouse thick ascending limb that is activated by ATP and protein kinase A, J Physiol, vol.485, pp.97-112, 1995.

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, vol.121, pp.287-300, 2003.
URL : https://hal.archives-ouvertes.fr/hal-02453227

A. Nissant, S. Lourdel, S. Baillet, M. Paulais, P. Marvao et al., Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp, Am J Physiol Renal Physiol, vol.287, pp.1233-1243, 2004.

A. Nissant, M. Paulais, S. Lachheb, S. Lourdel, and J. Teulon, Similar chloride channels in the connecting tubule and cortical collecting duct of the mouse kidney, Am J Physiol Renal Physiol, vol.290, pp.1421-1429, 2006.

J. Teulon, S. Lourdel, A. Nissant, M. Paulais, R. Guinamard et al., Imbert-Teboul, Exploration of the basolateral chloride channels in the renal tubule using the patch-clamp technique, Nephron Physiol, vol.99, pp.64-68, 2005.

S. Waldegger and T. J. Jentsch, Functional and structural analysis of ClC-K chloride channels involved in renal disease, J Biol Chem, vol.275, pp.24527-24533, 2000.

A. Diakov, K. Bera, M. Mokrushina, B. Krueger, and C. Korbmacher, Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels, J Physiol, vol.586, pp.4587-4608, 2008.

B. Krueger, S. Haerteis, L. Yang, A. Hartner, R. Rauh et al., Cholesterol depletion of the plasma membrane prevents activation of the epithelial sodium channel (ENaC) by SGK1, Cell Physiol Biochem, vol.24, pp.605-618, 2009.

N. Zerangue, B. Schwappach, Y. N. Jan, and L. Y. Jan, A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels, Neuron, vol.22, pp.537-548, 1999.

S. Uchida, S. Sasaki, T. Furukawa, M. Hiraoka, T. Imai et al., Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla, J Biol Chem, vol.269, p.19192, 1994.

S. Uchida, S. Sasaki, K. Nitta, K. Uchida, S. Horita et al., Localization and functional characterization of rat kidney-specific chloride channel, ClC-K1, J Clin Invest, vol.95, pp.104-113, 1995.

A. Liantonio, M. Pusch, A. Picollo, P. Guida, A. De-luca et al., 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, vol.15, pp.13-20, 2004.

S. Uchida, S. Sasaki, T. Furukawa, M. Hiraoka, T. Imai et al., Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla, J Biol Chem, vol.268, pp.3821-3824, 1993.

A. Diakov and C. Korbmacher, A novel pathway of epithelial sodium channel activation involves a serum-and glucocorticoid-inducible kinase consensus motif in the C terminus of the channel's alpha-subunit, J Biol Chem, vol.279, pp.38134-38142, 2004.

L. Feng, E. B. Campbell, Y. Hsiung, and R. Mackinnon, Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle, Science, vol.330, pp.635-641, 2010.

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

R. Dutzler, E. B. Campbell, M. Cadene, B. T. Chait, and R. Mackinnon, X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity, Nature, vol.415, pp.287-294, 2002.
URL : https://hal.archives-ouvertes.fr/hal-02150160

R. Dutzler, E. B. Campbell, and R. Mackinnon, Gating the selectivity filter in ClC chloride channels, Science, vol.300, pp.108-112, 2003.

A. G. Janssen, U. Scholl, C. Domeyer, D. Nothmann, A. Leinenweber et al., Disease-causing dysfunctions of barttin in Bartter syndrome type IV, J Am Soc Nephrol, vol.20, pp.145-153, 2009.

G. Zifarelli, A. Liantonio, A. Gradogna, A. Picollo, G. Gramegna et al., Identification of sites responsible for the potentiating effect of niflumic acid on ClC-Ka kidney chloride channels, Br J Pharmacol, vol.160, pp.1652-1661, 2010.

A. Liantonio, A. Picollo, E. Babini, G. Carbonara, G. Fracchiolla et al., Activation and inhibition of kidney CLC-K chloride channels by fenamates, Mol Pharmacol, vol.69, pp.165-173, 2006.

T. Y. Chen, Structure and function of clc channels, Annu Rev Physiol, vol.67, pp.809-839, 2005.

G. Rickheit, H. Maier, N. Strenzke, C. E. Andreescu, C. I. De-zeeuw et al., Endocochlear potential depends on Cl -channels: mechanism underlying deafness in Bartter syndrome IV, Embo J, vol.27, pp.2907-2917, 2008.

S. Uchida and S. Sasaki, Function of chloride channels in the kidney, Annu Rev Physiol, vol.67, pp.759-78, 2005.

N. Akizuki, S. Uchida, S. Sasaki, and F. Marumo, Impaired solute accumulation in inner medulla of Clcnk1-/-mice kidney, Am J Physiol Renal Physiol, vol.280, pp.79-87, 2001.

, Representative single-channel current recordings obtained at a holding potential (V hold ) of +50 mV from an outside-out patch. Bars above the traces indicate the presence of NaCl, NaI, or NaBr in the bath solution. The insets show segments of the same current traces on an expanded time scale. The segments correspond to the time intervals indicated by the black bars below the traces. The single-channel current amplitudes for Cl -, and Br -(i Cl-and i Br-, respectively) were determined as, Fig. 5. mClC-K1/mBarttin channel anion selectivity determined at the single-channel level in X. laevis oocytes A, B

. Fig, Whole-cell recordings of mClC-K1/mBarttin in HEK293-transfected cells. A, representative, original, whole-cell recordings obtained from cells expressing mClC, vol.6

, The pipette was filled with 150 mM Cl -. Cells were bathed in a solution at pH 7.4 or pH 9.0, or in a solution where 140 mM extracellular Cl -was replaced by I -. B, steady-state current-voltage relationships obtained from cells expressing mClC, K1/mBarttin channels

, 0, n = 4; I -, n = 4). C, steady-state current-voltage relationships obtained from cells expressing mClC-K1/mBarttin channels, Pipette was filled with 33 mM Cl -. Cells were bathed in physiological saline solution at pH 7.4 (n = 7) or pH 9.0 (n = 7)

, A, representative mClC-K1 current recordings in the cell-attached configuration obtained at various voltages for cells expressing mClC-K1 channels in the presence or absence of mBarttin. Binned current amplitude histograms for -85 mV membrane, Fig. 7. mClC-K1 single-channel activity in HEK293-transfected cells

, Cells were bathed in physiological saline solution, with high-Cl -solution in the pipette