ArticlePloS one2011
The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Intestinal current measurement detects age-dependent differences in CFTR function in rectal epithelium.Frontiers in pharmacology · 2025Article
- Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.Brain communications · 2024Article
- Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model.bioRxiv : the preprint server for biology · 2023Article
- Personalized CFTR Modulator Therapy forInternational journal of molecular sciences · 2023Article
- Splicing mutations in the CFTR gene as therapeutic targets.Gene therapy · 2022Review
- Assays of CFTR Function In Vitro, Ex Vivo and In Vivo.International journal of molecular sciences · 2022Review
- Personalized Medicine Based on Nasal Epithelial Cells: Comparative Studies with Rectal Biopsies and Intestinal Organoids.Journal of personalized medicine · 2021Article
- Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis.Journal of personalized medicine · 2021Review
- Intestinal current measurement and nasal potential difference to make a diagnosis of cases with inconclusiveBMJ open respiratory research · 2020Article
- Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon.Molecular genetics & genomic medicine · 2019Article
- Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis.United European gastroenterology journal · 2017Review
- Article
- Investigating CFTR and KCa3.1 Protein/Protein Interactions.PloS one · 2016Article
- Changing the Paradigm - Treating the Basic Defect in Cystic Fibrosis.Indian journal of pediatrics · 2015Review
- Aromatic-aromatic interactions between residues in KCa3.1 pore helix and S5 transmembrane segment control the channel gating process.The Journal of general physiology · 2014Article
- Article
- A functional CFTR assay using primary cystic fibrosis intestinal organoids.Nature medicine · 2013Article
- Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility.BMC gastroenterology · 2013Article
- Novel opportunities for CFTR-targeting drug development using organoids.Rare diseases (Austin, Tex.) · 2013Article
- Homozygous CFTR mutation M348K in a boy with respiratory symptoms and failure to thrive. Disease-causing mutation or benign alteration?European journal of pediatrics · 2012Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe identification of strategies to improve mutant CFTR function remains a key priority in the development of new treatments for cystic fibrosis (CF). Previous studies demonstrated that the K⁺ channel opener 1-ethyl-2-benzimidazolone (1-EBIO) potentiates CFTR-mediated Cl⁻ secretion in cultured cells and mouse colon. However, the effects of 1-EBIO on wild-type and mutant CFTR function in native human colonic tissues remain unknown.
methodsWe studied the effects of 1-EBIO on CFTR-mediated Cl⁻ secretion in rectal biopsies from 47 CF patients carrying a wide spectrum of CFTR mutations and 57 age-matched controls. Rectal tissues were mounted in perfused micro-Ussing chambers and the effects of 1-EBIO were compared in control tissues, CF tissues expressing residual CFTR function and CF tissues with no detectable Cl⁻ secretion.
resultsStudies in control tissues demonstrate that 1-EBIO activated CFTR-mediated Cl⁻ secretion in the absence of cAMP-mediated stimulation and potentiated cAMP-induced Cl⁻ secretion by 39.2±6.7% (P<0.001) via activation of basolateral Ca²⁺-activated and clotrimazole-sensitive KCNN4 K⁺ channels. In CF specimens, 1-EBIO potentiated cAMP-induced Cl⁻ secretion in tissues with residual CFTR function by 44.4±11.5% (P<0.001), but had no effect on tissues lacking CFTR-mediated Cl⁻ conductance.
conclusionsWe conclude that 1-EBIO potentiates Cl⁻secretion in native CF tissues expressing CFTR mutants with residual Cl⁻ channel function by activation of basolateral KCNN4 K⁺ channels that increase the driving force for luminal Cl⁻ exit. This mechanism may augment effects of CFTR correctors and potentiators that increase the number and/or activity of mutant CFTR channels at the cell surface and suggests KCNN4 as a therapeutic target for CF.
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