ArticleThe Journal of biological chemistry2010
Calcium inhibits paracellular sodium conductance through claudin-2 by competitive binding.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Inflammation-Induced Claudin-2 Up-Regulation Limits Pancreatitis Development by Enhancing Pancreatic Ductal Transport.Gastroenterology · 2026Article
- Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions.Science advances · 2025Article
- The Impact of Berberine on Intestinal Morphology, Microbes, and Immune Function of Broilers in Response to Necrotic Enteritis Challenge.BioMed research international · 2021Article
- Identification of a missense variant in CLDN2 in obstructive azoospermia.Journal of human genetics · 2019Article
- Gut permeability and mucosal inflammation: bad, good or context dependent.Mucosal immunology · 2017Review
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- Alterations in vitamin D metabolite, parathyroid hormone and fibroblast growth factor-23 concentrations in sclerostin-deficient mice permit the maintenance of a high bone mass.The Journal of steroid biochemistry and molecular biology · 2015Review
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- Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis.Mucosal immunology · 2014Article
- Reduced renal calcium excretion in the absence of sclerostin expression: evidence for a novel calcium-regulating bone kidney axis.Journal of the American Society of Nephrology : JASN · 2014Review
- Regulation of paracellular permeability: factors and mechanisms.Molecular biology reports · 2013Review
- Claudin interactions in and out of the tight junction.Tissue barriers · 2013Review
- A connected tale of claudins from the renal duct to the sensory system.Tissue barriers · 2013Review
- Claudins and the modulation of tight junction permeability.Physiological reviews · 2013Review
- Effects of a high-sodium diet on renal tubule Ca2+ transporter and claudin expression in Wistar-Kyoto rats.BMC nephrology · 2012Article
- Blood-brain barrier dysfunction and recovery after ischemic stroke.Progress in neurobiologyReview
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Claudins form paracellular pores at the tight junction in epithelial cells. Profound depletion of extracellular calcium is well known to cause loosening of the tight junction with loss of transepithelial resistance. However, moderate variations in calcium concentrations within the physiological range can also regulate transepithelial permeability. To investigate the underlying molecular mechanisms, we studied the effects of calcium on the permeability of claudin-2, expressed in an inducible MDCK I cell line. We found that in the physiological range, calcium acts as a reversible inhibitor of the total conductance and Na(+) permeability of claudin-2, without causing changes in tight junction structure. The effect of calcium is enhanced at low Na(+) concentrations, consistent with a competitive effect. Furthermore, mutation of an intrapore negatively charged binding site, Asp-65, to asparagine partially abrogated the inhibitory effect of calcium. This suggests that calcium competes with Na(+) for binding to Asp-65. Other polyvalent cations had similar effects, including La(3+), which caused severe and irreversible inhibition of conductance. Brownian dynamics simulations demonstrated that such inhibition can be explained if Asp-65 has a relatively high charge density, thus favoring binding of Ca(2+) over that of Na(+), reducing Ca(2+) permeation by inhibiting its dissociation from this site, and decreasing Na(+) conductance through repulsive electrostatic interaction with Ca(2+). These findings may explain why hypercalcemia inhibits Na(+) reabsorption in the proximal tubule of the kidney.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.