The ATP‐sensitivity of K+ channels in rat pancreatic B‐cells is modulated by ADP
Abstract
ATP-sensitive K+ channels in inside-out membrane patches from dispersed rat pancreatic B-cells were studied using patch-clamp methods. The dose-response curve for ATP-induced channel inhibition was shifted to higher concentrations in the presence of ADP (2 mM). In glucose-free solution, the total intracellular concentration of ATP was 3.8 mM and of ADP 1.5 mM; glucose (20 mM) increased ATP and decreased ADP by approx. 40%. These results suggest that both ADP and ATP may be involved in regulating the activity of the glucose-sensitive K+ channel in intact B-cells.
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Metabolic regulation of the KATP channel is mediated by changes in intracellular concentrations of ATP and MgADP, which inhibit and stimulate the channel, respectively.
“Metabolic regulation of the channel is mediated by changes in the intracellular concentrations of ATP and MgADP, which inhibit and stimulate the channel, respectively (127, 163, 328).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [328]
The lower ATP sensitivity of the KATP channel in the intact cell is due to the presence of intracellular MgADP, and glucose acts by changing the relative concentrations of ATP and ADP.
“There is considerable evidence that the lower ATP sensitivity of the KATP channel in the intact cell is due to the presence of intracellular MgADP, as in this configuration KATP channel activity persists at intracellular ATP concentrations normally associated with nearly complete inhibition of channel activity (72, 163, 328, 366). This suggests that glucose acts by changing the relative Concentra”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [328]
In a cell with a volume of 1 pl, this corresponds to an average ADP concentration of 0.5 mM, sufficient to activate the KATP channel even in the presence of mM ATP.
“In a cell with a volume of 1 pl, this would correspond to an average ADP concentration of 0.5 mM, sufficient to activate the KATP channel even in the presence of mM ATP (328).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [328]
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 · 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
Self-citationSchwanstecher, C., Neugebauer, B., Schulz, M., & Schwanstecher, M. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s363 · Cited by 62 · see citing works
- Authors
- Kakei, M., Kelly, R. P., Ashcroft, S. J. H., & Ashcroft, F. M.
- Affiliations
- University of Oxford (GB)
- John Radcliffe Hospital (GB)
- Corresponding author
- Ashcroft, Frances M.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1986-11-10
- Volume
- 208
- Issue
- 1
- Pages
- 63-66
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2022092956
- Cited by
- 241
- References
- 1
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 2 · 2018: 3 · 2017: 4 · 2016: 1 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Medical Research Council
- 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 › Physiology › Adenosine and Purinergic Signaling
- Keywords
- ATP-sensitive potassium channels, ADP, pancreatic beta cells
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Animals, Glucose, Ion Channels, Islets of Langerhans, Potassium, Rats, In Vitro Techniques
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