ArticleProceedings of the National Academy of Sciences of the United States of America2002
Nucleotides and phospholipids compete for binding to the C terminus of KATP channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 130 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.Molecular biology of the cell · 2024Article
- Mechanisms and Functions of Sweet Reception in Oral and Extraoral Organs.International journal of molecular sciences · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Article
- The dynamic interplay of PIPThe Journal of physiology · 2022Article
- Inward Rectifier Potassium Channels: Membrane Lipid-Dependent Mechanosensitive Gates in Brain Vascular Cells.Frontiers in cardiovascular medicine · 2022Review
- Pituitary Adenylate Cyclase Activating Polypeptide Inhibits ANeuroscience · 2021Article
- A review of TNP-ATP in protein binding studies: benefits and pitfalls.Biophysical reports · 2021Review
- From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels.Journal of molecular biology · 2021Review
- Phosphatidylinositol-3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells.Journal of neurochemistry · 2021Article
- Dictyostelium discoideum as a non-mammalian biomedical model.Microbial biotechnology · 2021Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2020Review
- With PIPs, you get ZIPs and blips.The Journal of general physiology · 2019Article
- 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
- Biphasic voltage-dependent inactivation of human NaThe Journal of physiology · 2018Article
- ATP competes with PIP2 for binding to gelsolin.PloS one · 2018Article
- Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Inwardly rectifying, ATP-sensitive K+ channels (K(ATP)) couple metabolism to either cell excitability (Kir6.x) or potassium secretion (Kir1.1). Phosphatidylinositol phospholipids, like PI(4,5)P2, antagonize nucleotide inhibition of K(ATP) channels enhancing the coupling of metabolic events to cell electrical or transport activity. The mechanism by which phospholipids relieve ATP block is unclear. We have shown that maltose-binding fusion proteins (MBP) containing the COOH termini of K(ATP) channels (Kir1.1, Kir6.1, and Kir6.2) form functional tetramers that directly bind at least two ATP molecules with negative cooperativity. Here we show that purified phosphatidylinositol phospholipids compete for 2,4,6,-trinitrophenyl (TNP)-ATP binding to the COOH termini of K(ATP) channels with EC50 values for PIP2 between 6-8 microM. The phospholipid potency profile was PIP3 > PIP2 = PIP > PI, suggesting that net phospholipid charge was important. A role for head group charge was supported by polycations (neomycin, spermine, and polylysine) reversing the effect of PIP2 on TNP-ATP binding to the Kir1.1 channel COOH terminal fusion protein. In contrast, the water-soluble charged hydrolytic product of PIP2, inositol(1,4,5)P3 (IP3), had no effect on TNP-ATP binding, suggesting that the acyl chain of PIP2 was also necessary for its effect on TNP-ATP binding. Indeed, neutral and charged lipids had weak, but significant, effects on TNP-ATP binding. Whereas microM concentrations of PIP2 could compete with TNP-ATP, we found that mM concentrations of MgATP were required to compete with PIP2 for binding to these K(ATP) channel COOH termini. Thus the COOH termini of K(ATP) channels form a nucleotide- and phospholipid-modulated channel gate on which ATP and phospholipids compete for binding.
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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.