ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Murine and human CFTR exhibit different sensitivities to CFTR potentiators.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Chronic hyperglycemia aggravates lung function in aAmerican journal of physiology. Lung cellular and molecular physiology · 2024Article
- Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.The Journal of clinical investigation · 2023Article
- A transistor model for the cystic fibrosis transmembrane conductance regulator.Biophysical reports · 2023Article
- CFTR Modulators Restore Acidification of Autophago-Lysosomes and Bacterial Clearance in Cystic Fibrosis Macrophages.Frontiers in cellular and infection microbiology · 2022Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Electrophysiological Approaches for the Study of Ion Channel Function.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Characterization of two rat models of cystic fibrosis-KO and F508del CFTR-Generated by Crispr-Cas9.Animal models and experimental medicine · 2019Article
- VX-770-mediated potentiation of numerous human CFTR disease mutants is influenced by phosphorylation level.Scientific reports · 2019Article
- Differential thermostability and response to cystic fibrosis transmembrane conductance regulator potentiators of human and mouse F508del-CFTR.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- Article
- A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease.The EMBO journal · 2019Article
- Functional characterization reveals that zebrafish CFTR prefers to occupy closed channel conformations.PloS one · 2018Article
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Potentiators exert distinct effects on human, murine, and Xenopus CFTR.American journal of physiology. Lung cellular and molecular physiology · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Development of therapeutic molecules with clinical efficacy as modulators of defective CFTR includes efforts to identify potentiators that can overcome or repair the gating defect in mutant CFTR channels. This has taken a great leap forward with the identification of the potentiator VX-770, now available to patients as "Kalydeco." Other small molecules with different chemical structure also are capable of potentiating the activity of either wild-type or mutant CFTR, suggesting that there are features of the protein that may be targeted to achieve stimulation of channel activity by structurally diverse compounds. However, neither the mechanisms by which these compounds potentiate mutant CFTR nor the site(s) where these compounds bind have been identified. This knowledge gap partly reflects the lack of appropriate experimental models to provide clues toward the identification of binding sites. Here, we have compared the channel behavior and response to novel and known potentiators of human CFTR (hCFTR) and murine (mCFTR) expressed in Xenopus oocytes. Both hCFTR and mCFTR were blocked by GlyH-101 from the extracellular side, but mCFTR activity was increased with GlyH-101 applied directly to the cytoplasmic side. Similarly, glibenclamide only exhibited a blocking effect on hCFTR but both blocked and potentiated mCFTR in excised membrane patches and in intact oocytes. The clinically used CFTR potentiator VX-770 transiently increased hCFTR by ∼13% but potentiated mCFTR significantly more strongly. Our results suggest that mCFTR pharmacological sensitivities differ from hCFTR, which will provide a useful tool for identifying the binding sites and mechanism for these potentiators.
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