Cloning and functional expression of the cDNA encoding a novel ATP‐sensitive potassium channel subunit expressed in pancreatic β‐cells, brain, heart and skeletal muscle
Open accessAbstract
A cDNA clone encoding an inwardly‐rectifying potassium channel subunit (Kir6.2) was isolated from an insulinoma cDNA library. The mRNA is strongly expressed in brain, skeletal muscle, cardiac muscle and in insulinoma cells, weakly expressed in lung and kidney and not detectable in spleen, liver or testis. Heterologous expression of Kir6.2 in HEK293 cells was only observed when the cDNA was cotransfected with that of the sulphonylurea receptor (SUR). Whole‐cell Kir6.2/SUR currents were K+‐selective, time‐independent and showed weak inward rectification. They were blocked by external barium (5 mM), tolbutamide (K d = 4.5 μ M) or quinine (20 μ M) and by 5 mM intracellular ATP. The single‐channel conductance was 73 pS. Single‐channel activity was voltage‐independent and was blocked by 1 mM intracellular ATP or 0.5 mM tolbutamide. We conclude that the Kir6.2/SUR channel complex comprises the ATP‐sensitive K‐channel.
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The KATP channel is an octameric complex of 4 pore-forming Kir6.2 subunits and 4 regulatory SUR1 subunits.
“The successful cloning and molecular characterization of the KATP channel revealed it is an octameric complex of 4 pore-forming Kir6.2 s and 4 regulatory SUR1 subunits (4, 302, 583).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [583]
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- Authors
- Sakura, H., Ämmälä, C., Smith, P. A., Gribble, F. M., & Ashcroft, F. M.
- Affiliations
- University of Oxford (GB)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1995-12-27
- Volume
- 377
- Issue
- 3
- Pages
- 338-344
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2050342883
- Cited by
- 411
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 9
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- Kir6.2, ATP-sensitive potassium channels, sulfonylurea receptor, inwardly rectifying potassium channels, cDNA cloning, insulinoma, pancreatic beta cells, heterologous expression, barium block, tolbutamide, quinine, single-channel conductance, ATP-gated ion channels
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Brain, Electric Conductivity, Electrophysiology, Insulinoma, Islets of Langerhans, Molecular Sequence Data, Myocardium, Receptors, Drug, Tissue Distribution, Transfection, Potassium Channels, Gene Library, Sequence Homology, Amino Acid, Sequence Analysis, DNA, DNA, Complementary, Muscle, Skeletal, ATP-Binding Cassette Transporters, Potassium Channels, Inwardly Rectifying, Potassium Channel Blockers, Mice, Sulfonylurea Receptors
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