ArticleThe Journal of biological chemistry2008
Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Clinical Report and Genetic Analysis of a Patient With Congenital Hyperinsulinism Hyperammonemia Caused by a Novel Missense Mutation in the Structural Domain of the Isoform of the GLUD1 Gene.Clinical case reports · 2026Article
- Article
- Mechanistic insights on KATP channel regulation from cryo-EM structures.The Journal of general physiology · 2023Review
- KFrontiers in endocrinology · 2023Review
- Pituitary stalk interruption syndrome and liver cirrhosis associated with diabetes and an inactivatingFrontiers in endocrinology · 2023Review
- CL-705G: a novel chemical Kir6.2-specific KFrontiers in pharmacology · 2023Article
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- Ligand-mediated Structural Dynamics of a Mammalian Pancreatic KJournal of molecular biology · 2022Article
- Sirolimus in infants with congenital hyperinsulinism (CHI) - a single-centre experience.European journal of pediatrics · 2022Article
- Structural Determinants of Insulin Release: Disordered N-Terminal Tail of Kir6.2 Affects Potassium Channel Dynamics through Interactions with Sulfonylurea Binding Region in a SUR1 Partner.The journal of physical chemistry. B · 2020Article
- Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model.Translational neuroscience · 2020Article
- Novel dominant KAmerican journal of medical genetics. Part A · 2019Article
- Disease Associated Mutations in KBiomolecules · 2019Review
- Cryo-electron microscopy structures and progress toward a dynamic understanding of KThe Journal of general physiology · 2018Review
- The role of KActa pharmacologica Sinica · 2018Review
- Genetic Testing of Maturity-Onset Diabetes of the Young Current Status and Future Perspectives.Frontiers in endocrinology · 2018Review
- Anti-diabetic drug binding site in a mammalian KeLife · 2017Article
- Control of Kir channel gating by cytoplasmic domain interface interactions.The Journal of general physiology · 2017Article
- Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism.The Journal of biological chemistry · 2015Article
- Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels.Frontiers in physiology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The inwardly rectifying potassium channel Kir6.2 is the pore-forming subunit of the ATP-sensitive potassium (K(ATP)) channel, which controls insulin secretion by coupling glucose metabolism to membrane potential in beta-cells. Loss of channel function because of mutations in Kir6.2 or its associated regulatory subunit, sulfonylurea receptor 1, causes congenital hyperinsulinism (CHI), a neonatal disease characterized by persistent insulin secretion despite severe hypoglycemia. Here, we report a novel K(ATP) channel gating defect caused by CHI-associated Kir6.2 mutations at arginine 301 (to cysteine, glycine, histidine, or proline). These mutations in addition to reducing channel expression at the cell surface also cause rapid, spontaneous current decay, a gating defect we refer to as inactivation. Based on the crystal structures of Kir3.1 and KirBac1.1, Arg-301 interacts with several residues in the neighboring Kir6.2 subunit. Mutation of a subset of these residues also induces channel inactivation, suggesting that the disease mutations may cause inactivation by disrupting subunit-subunit interactions. To evaluate the effect of channel inactivation on beta-cell function, we expressed an alternative inactivation mutant R301A, which has equivalent surface expression efficiency as wild type channels, in the insulin-secreting cell line INS-1. Mutant expression resulted in more depolarized membrane potential and elevated insulin secretion at basal glucose concentration (3 mm) compared with cells expressing wild type channels, demonstrating that the inactivation gating defect itself is sufficient to cause loss of channel function and hyperinsulinism. Our studies suggest the importance of Kir6.2 subunit-subunit interactions in K(ATP) channel gating and function and reveal a novel gating defect underlying CHI.
Indexed as
Identifiers
What OpenQuestion holds
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.