Physiology and Pathophysiology of ClC-K/barttin Channels

ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

• Publication year

  2010

• Venue

  Front. Physio.

• Publication date

  2010-09-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fphys.2010.00155PMID 21423394PMCID 3059957
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2010cited by this paper
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  2010influential reference
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  2010cited by this paper
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  2010influential reference
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  2010influential reference
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009influential reference
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  2008cited by this paper
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  2008cited by this paper
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  2008influential reference
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  2008cited by this paper
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  2008cited by this paper
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  2008influential reference
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  2008cited by this paper
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  2008influential reference
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  2008influential reference
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2006cited by this paper
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  2006influential reference
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  2006cited by this paper
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  2006cited by this paper
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  2006influential reference
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  2006influential reference
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  2006cited by this paper
• A compound heterozygous mutation in the BSND gene detected in Bartter syndrome type IV

  2006influential reference
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  2006cited by this paper
• Carboxy-terminal truncations modify the outer pore vestibule of muscle chloride channels.

  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2005influential reference
• Quantitative Analysis of the Voltage-dependent Gating of Mouse Parotid ClC-2 Chloride Channel

  2005cited by this paper
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  2005influential reference
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  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
• A common sequence variation of the CLCNKB gene strongly activates ClC-Kb chloride channel activity.

  2004cited by this paper
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  2004cited by this paper
• Salt wasting and deafness resulting from mutations in two chloride channels.

  2004cited by this paper
• Activating Mutation of the Renal Epithelial Chloride Channel ClC-Kb Predisposing to Hypertension

  2004cited by this paper
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  2003influential reference
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  2003cited by this paper
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  2003cited by this paper
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  2003cited by this paper
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  2003influential reference
• Human CLC-KB gene promoter drives the EGFP expression in the specific distal nephron segments and inner ear.

  2002cited by this paper
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  2002cited by this paper
• Barttin increases surface expression and changes current properties of ClC-K channels

  2002cited by this paper
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  2002influential reference
• Male germ cells and photoreceptors, both dependent on close cell–cell interactions, degenerate upon ClC‐2 Cl− channel disruption

  2001influential reference
• Barttin is a Cl- channel β-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion

  2001cited by this paper
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  2001cited by this paper
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  2001influential reference
• Chloride channels in the loop of Henle.

  2001cited by this paper
• Pores Formed by Single Subunits in Mixed Dimers of Different CLC Chloride Channels*

  2001cited by this paper
• Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.

  2001cited by this paper
• Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure

  2001cited by this paper
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  2001cited by this paper
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  2000influential reference
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  2000cited by this paper
• Functional and Structural Analysis of ClC-K Chloride Channels Involved in Renal Disease*

  2000influential reference
• The Muscle Chloride Channel ClC-1 Has a Double-Barreled Appearance that Is Differentially Affected in Dominant and Recessive Myotonia

  1999cited by this paper
• Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel

  1999cited by this paper
• Localization of rat CLC-K2 chloride channel mRNA in the kidney.

  1999cited by this paper
• Mutational Analysis Demonstrates That ClC-4 and ClC-5 Directly Mediate Plasma Membrane Currents*

  1999cited by this paper
• ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells.

  1998cited by this paper
• I(sK) Channel in Strial Marginal Cells. Voltage-Dependence, Ion-Selectivity, Inhibition by 293B and Sensitivity to Clofilium.

  1997cited by this paper
• Localization and induction by dehydration of ClC-K chloride channels in the rat kidney.

  1997cited by this paper
• Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III

  1997cited by this paper
• Pore-forming segments in voltage-gated chloride channels

  1997cited by this paper
• A common molecular basis for three inherited kidney stone diseases

  1996cited by this paper
• Concentration and pH dependence of skeletal muscle chloride channel ClC‐1.

  1996cited by this paper
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  1996cited by this paper
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  1995influential reference
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  1995cited by this paper
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  1995cited by this paper
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  1995cited by this paper
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  1994cited by this paper
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  1994influential reference
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  1994cited by this paper
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  1993influential reference
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  1993cited by this paper

• Mechanism of Gating and Isoform-Specific Inhibition in Renal CLC Chloride Channels

  2026cites this paper
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  2026cites this paper
• Clinical use of Loop Diuretics Acting on Symporters

  2025cites this paper
• Expanding Genotype–Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss

  2023influential citation
• Inhibitory effect of S-nitroso-N-acetylpenicillamine on the basolateral 10-pS Cl- channel in thick ascending limb

  2023cites this paper
• Small Molecules Targeting Kidney ClC-K Chloride Channels: Applications in Rare Tubulopathies and Common Cardiovascular Diseases

  2023cites this paper
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  2023cites this paper
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  2022cites this paper
• AN OVERVIEW ON BARTTER SYNDROMES: LITERATURE REVIEW

  2021cites this paper
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  2021cites this paper
• DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
• New Insights into the Mechanism of NO3 - Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein Family.

  2019cites this paper
• Reconstitution and NMR Characterization of the Ion-Channel Accessory Subunit Barttin in Detergents and Lipid-Bilayer Nanodiscs

  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018influential citation
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  2017influential citation
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
• Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH

  2016influential citation
• Hearing status in Egyptian children with nephrotic syndrome

  2016cites this paper
• Caractérisation des canaux potassiques du tubule contourné proximal et des propriétés régulatrices des canaux chlorure de la membrane basolatérale des cellules intercalaires du tubule connecteur

  2015cites this paper
• Tryptophan Scanning Mutagenesis Identifies the Molecular Determinants of Distinct Barttin Functions*

  2015cites this paper
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  2015cites this paper
• Identification and characterization of the zebrafish ClC-2 chloride channel orthologs

  2015cites this paper
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  2015cites this paper
• ClC-K chloride channels: emerging pathophysiology of Bartter syndrome type 3.

  2015cites this paper
• Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China

  2015cites this paper
• Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking*

  2015cites this paper
• Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional*

  2015cites this paper
• Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review

  2015influential citation
• Regulatory–auxiliary subunits of CLC chloride channel–transport proteins

  2015cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
• Characterization of the mouse ClC-K1/Barttin chloride channel.

  2013influential citation
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  2013cites this paper
• Analyse fonctionnelle de nouvelles mutations pathogènes du canal chlorure CLC-KB impliquées dans le syndrome de Bartter

  2012cites this paper
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  2012cites this paper
• Consultants

  2011cites this paper
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  2011cites this paper
• ION CHANNELS

  2011cites this paper
• ENZYMES

  2011cites this paper
• TRANSPORTERS

  2011cites this paper
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  2011cites this paper
• CATALYTIC RECEPTORS

  2011cites this paper
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  2011cites this paper
• Channels in the loop of henle of the Kidney and the stria vasCularis of the inner ear

  2010influential citation