Membrane Phospholipid Control of Nucleotide Sensitivity of K ATP Channels
Abstract
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple cell metabolism to electrical activity. Phosphatidylinositol phosphates (PIPs) profoundly antagonized ATP inhibition of KATP channels when applied to inside-out membrane patches. It is proposed that membrane-incorporated PIPs can bind to positive charges in the cytoplasmic region of the channel's Kir6.2 subunit, stabilizing the open state of the channel and antagonizing the inhibitory effect of ATP. The tremendous effect of PIPs on ATP sensitivity suggests that in vivo alterations of membrane PIP levels will have substantial effects on KATP channel activity and hence on the gain of metabolism-excitation coupling.
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KATP channels are regulated by lipids such as phosphatidyl inositol bisphosphate (PIP2) and long-chain acyl CoAs, which stimulate channel opening and reduce its ATP sensitivity.
“KATP channels are also regulated by lipids such as phosphatidyl inositol bisphosphate (PIP2) and long-chain acyl CoAs (e.g. oleoyl coA), which stimulate channel opening and reduce its ATP sensitivity (229, 622).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [622]
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References 17 · Cited by 559
- Authors
- Shyng, S.-L., & Nichols, C. G.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Nichols, C. G.
- Venue
- Science
- Published
- 1998-11-06
- Volume
- 282
- Issue
- 5391
- Pages
- 1138-1141
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1965209959
- Cited by
- 559
- References
- 17
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 8 · 2014: 16 · 2013: 23 · 2012: 14
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 45742, R01HL045742)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- ATP-sensitive potassium channels, phosphoinositides, membrane phospholipids, ATP inhibition
- MeSH terms
- Adenosine Triphosphate, Animals, Binding Sites, Cell Line, Islets of Langerhans, Mutation, Myocardium, Receptors, Drug, Recombinant Fusion Proteins, Potassium Channels, Phosphatidylinositol Phosphates, Patch-Clamp Techniques, ATP-Binding Cassette Transporters, Phosphatidylinositol 4,5-Diphosphate, COS Cells, Potassium Channels, Inwardly Rectifying, Sulfonylurea Receptors
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