ArticleGastroenterology2012
Severe defects in absorptive ion transport in distal colons of mice that lack ClC-2 channels.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- ClC-2 Contributes to Hypotonicity-Induced Adrenal Aldosterone Secretion.Acta physiologica (Oxford, England) · 2026Article
- Lubiprostone is non-selective activator of cAMP-gated ion channels and Clc-2 has a minor role in its prosecretory effect in intestinal epithelial cells.Molecular pharmacology · 2022Article
- Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism.Nature communications · 2019Article
- Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents.Frontiers in pharmacology · 2017Review
- Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome.Molecular and cellular pediatrics · 2016Article
- Opioid-induced constipation: advances and clinical guidance.Therapeutic advances in chronic disease · 2016Review
- Gating the glutamate gate of CLC-2 chloride channel by pore occupancy.The Journal of general physiology · 2016Article
- Discovery of CLC transport proteins: cloning, structure, function and pathophysiology.The Journal of physiology · 2015Review
- Regulatory-auxiliary subunits of CLC chloride channel-transport proteins.The Journal of physiology · 2015Review
- Identification and characterization of the zebrafish ClC-2 chloride channel orthologs.Pflugers Archiv : European journal of physiology · 2015Article
- Lubiprostone in constipation: clinical evidence and place in therapy.Therapeutic advances in chronic disease · 2015Review
- Epithelia of the ovine and bovine forestomach express basolateral maxi-anion channels permeable to the anions of short-chain fatty acids.Pflugers Archiv : European journal of physiology · 2014Article
- Chloride channelopathies of ClC-2.International journal of molecular sciences · 2013Review
- Chloride channel ClC-2 is a key factor in the development of DSS-induced murine colitis.Inflammatory bowel diseases · 2013Article
- Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.American journal of physiology. Lung cellular and molecular physiology · 2013Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe fluid secretion model predicts that intestinal obstruction disorders can be alleviated by promoting epithelial Cl(-) secretion. The adenosine 3',5'-cyclic monophosphate (cAMP)-activated anion channel CFTR mediates Cl(-)-dependent fluid secretion in the intestine. Although the role of the ClC-2 channel has not been determined in the intestine, this voltage-gated Cl(-) channel might compensate for the secretory defects observed in patients with cystic fibrosis and other chronic constipation disorders. We investigated whether mice that lack ClC-2 channels (Clcn2(-/-)) have defects in intestinal ion transport.
methodsImmunolocalization and immunoblot analyses were used to determine the cellular localization and the amount of ClC-2 expressed in mouse early distal colon (EDC) and late distal colon (LDC). Colon sheets from wild-type and Clcn2(-/-) littermates were mounted in Ussing chambers to determine transepithelial bioelectrical parameters and Na(+), K(+), and Cl(-) fluxes.
resultsExpression of ClC-2 was higher in the basolateral membrane of surface cells in the EDC compared with the LDC, with little expression in crypts. Neither cAMP nor Ca(2+)-induced secretion of Cl(-) was affected in the EDC or LDC of Clcn2(-/-) mice, whereas the amiloride-sensitive short-circuit current was increased approximately 3-fold in Clcn2(-/-) EDC compared with control littermates. Conversely, electroneutral Na(+), K(+), and Cl(-) absorption was dramatically reduced in colons of Clcn2(-/-) mice.
conclusionsBasolateral ClC-2 channels are required for colonic electroneutral absorption of NaCl and KCl. The increase in the amiloride-sensitive short-circuit current in Clcn2(-/-) mice revealed a compensatory mechanism that is activated in the colons of mice that lack the ClC-2 channel.
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Registered trials
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