ArticleThe Journal of general physiology1998
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
Article in The Journal of general physiology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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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.
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Who cites it
88 citing papers in PubMed, 173 citations in OpenAlex.
- Rapid Characterization of the Functional and Pharmacological Consequences of Cantú Syndrome KThe Journal of pharmacology and experimental therapeutics · 2023Article
- Mechanistic insights on KATP channel regulation from cryo-EM structures.The Journal of general physiology · 2023Review
- Oxidation Driven Reversal of PIPFunction (Oxford, England) · 2023Article
- The dynamic interplay of PIPThe Journal of physiology · 2022Article
- Molecular structure of an open human KProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Evaluating inositol phospholipid interactions with inward rectifier potassium channels and characterising their role in disease.Communications chemistry · 2020Article
- New insights into KNature reviews. Endocrinology · 2020Review
- Palmitoylation of the KProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Conformational changes upon gating of KirBac1.1 into an open-activated state revealed by solid-state NMR and functional assays.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nucleotide inhibition of the pancreatic ATP-sensitive K+ channel explored with patch-clamp fluorometry.eLife · 2020Article
- Computational Identification of Novel Kir6 Channel Inhibitors.Frontiers in pharmacology · 2019Article
- Cryo-electron microscopy structures and progress toward a dynamic understanding of KThe Journal of general physiology · 2018Review
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Control of Kir channel gating by cytoplasmic domain interface interactions.The Journal of general physiology · 2017Article
- Hyperinsulinemic Hypoglycemia - The Molecular Mechanisms.Frontiers in endocrinology · 2016Review
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
- A Conserved Residue Cluster That Governs Kinetics of ATP-dependent Gating of Kir6.2 Potassium Channels.The Journal of biological chemistry · 2015Article
- Sulfonylureas suppress the stimulatory action of Mg-nucleotides on Kir6.2/SUR1 but not Kir6.2/SUR2A KATP channels: a mechanistic study.The Journal of general physiology · 2014Article
- Decomposition of slide helix contributions to ATP-dependent inhibition of Kir6.2 channels.The Journal of biological chemistry · 2013Article
- Molecular mechanisms of chloroquine inhibition of heterologously expressed Kir6.2/SUR2A channels.Molecular pharmacology · 2012Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The beta cell KATP channel is an octameric complex of four pore-forming subunits (Kir6.2) and four regulatory subunits (SUR1). A truncated isoform of Kir6.2 (Kir6.2DeltaC26), which expresses independently of SUR1, shows intrinsic ATP sensitivity, suggesting that this subunit is primarily responsible for mediating ATP inhibition. We show here that mutation of C166, which lies at the cytosolic end of the second transmembrane domain, to serine (C166S) increases the open probability of Kir6.2DeltaC26 approximately sevenfold by reducing the time the channel spends in a long closed state. Rundown of channel activity is also decreased. Kir6.2DeltaC26 containing the C166S mutation shows a markedly reduced ATP sensitivity: the Ki is reduced from 175 microM to 2.8 mM. Substitution of threonine, alanine, methionine, or phenylalanine at position C166 also reduced the channel sensitivity to ATP and simultaneously increased the open probability. Thus, ATP does not act as an open channel blocker. The inhibitory effects of tolbutamide are reduced in channels composed of SUR1 and Kir6.2 carrying the C166S mutation. Our results are consistent with the idea that C166 plays a role in the intrinsic gating of the channel, possibly by influencing a gate located at the intracellular end of the pore. Kinetic analysis suggests that the apparent decrease in ATP sensitivity, and the changes in other properties, observed when C166 is mutated is largely a consequence of the impaired transition from the open to the long closed state.
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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.