KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP.
Abstract
In pancreatic beta-cells, inhibition of K(ATP)-channels plays a pivotal role in signal transduction of glucose-induced insulin release. However, the extreme sensitivity of K(ATP)-channels to its ligand ATP as found in inside-out patches is not directly compatible with modulation of these channels at physiological [ATP](i). We studied K(ATP)-channel sensitivity to ATP in beta-cells in dispersed culture and in fresh pancreatic tissue slices. Physiological [ATP](i) blocks more than 99% of K(ATP)-channels in cultured beta-cells, while only 90% in beta-cells in slices, indicating reduced sensitivity to ATP in the fresh slices. Applying cytosolic factors like ADP, phosphatidylinositol-4,5-bisphosphate (PIP(2)) or oleoyl-CoA did not restore the K(ATP)-channel sensitivity in cultured beta-cells. Our data suggest that interaction between SUR1 and Kir6.2 subunit of the K(ATP)-channel could be a factor in sensitivity modulation. Tissue slices are the first beta-cell preparation to study direct K(ATP)-channel modulation by physiological [ATP](i).
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The MgATP sensitivity of the KATP channel is much lower in the whole-cell configuration, with half-maximal inhibition at 0.4-0.8 mM rather than 0.01 mM as in excised patches.
“Resolution of this puzzle is provided by the fact that the MgATP sensitivity of the channel is much lower when measured in the whole-cell configuration: inhibition is half-maximal at 0.4-0.8 mM rather than 0.01 mM as in excised patches (641).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [641]
Cites
Intracellular ATP directly blocks K+ channels in pancreatic B-cells
Cook, D. L., & Hales, N. (1984) · Nature · doi:10.1038/311271a0 · Cited by 1,208 · cited 2× · see citing works
“Millimolar [ATP] i is at least two order of magnitude above the ATP concentration needed to inhibit KATP-channel in inside-out patches (Cook and Hales 1984).”
Gloyn, A. L., Pearson, E. R., Antcliff, J. F., Proks, P., Bruining, G. J., Slingerland, A. S., Howard, N., Srinivasan, S., Silva, J. M. C. L., Molnes, J., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032922 · Cited by 1,137 · see citing works
Voltage‐gated and resting membrane currents recorded from B‐cells in intact mouse pancreatic islets
Göpel, S., Kanno, T., Barg, S., Galvanovskis, J., & Rorsman, P. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00717.x · Cited by 226 · see citing works
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Yang, S.-B., Tien, A.-C., Boddupalli, G., Xu, A. W., Jan, Y. N., & Jan, L. Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.043 · Cited by 242 · see citing works
Self-citationMontefusco, F., & Pedersen, M. G. (2015) · The Journal of Physiology · doi:10.1113/jp270777 · Cited by 35 · see citing works
- Authors
- Speier, S., Yang, S.-B., Sroka, K., Rose, T., & Rupnik, M.
- Affiliations
- European Neuroscience Institute Göttingen (DE)
- Corresponding author
- Rupnik, M.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 230
- Issue
- 1-2
- Pages
- 51-58
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2124790004
- Cited by
- 53
- References
- 3
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 1 · 2017: 6 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 4
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Funders
- European Commission
- Max-Planck-Gesellschaft
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- ATP-sensitive potassium channels, pancreatic beta cells, ATP sensitivity, intracellular ATP, tissue slices, SUR1, Kir6.2, glucose-stimulated insulin secretion, ADP, phosphatidylinositol 4,5-bisphosphate, oleoyl-CoA, channel modulation
- MeSH terms
- Adenosine Triphosphate, Animals, Cells, Cultured, Humans, Islets of Langerhans, Male, Potassium Channels, Inwardly Rectifying, Tissue Culture Techniques, Mice
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