ATP Sensitivity of the ATP-Sensitive K+ Channel in Intact and Permeabilized Pancreatic β-Cells
Open accessAbstract
ATP-sensitive K+ channels (KATP channels) couple cell metabolism to electrical activity and thereby to physiological processes such as hormone secretion, muscle contraction, and neuronal activity. However, the mechanism by which metabolism regulates KATP channel activity, and the channel sensitivity to inhibition by ATP in its native environment, remain controversial. Here, we used α-toxin to permeabilize single pancreatic β-cells and measure KATP channel ATP sensitivity. We show that the channel ATP sensitivity is approximately sevenfold lower in the permeabilized cell than in the inside-out patch and that this is caused by interaction of Mg-nucleotides with the nucleotide-binding domains of the SUR1 subunit of the channel. The ATP sensitivity observed in permeabilized cells accounts quantitatively for KATP channel activity in intact cells. Thus, our results show that the principal metabolic regulators of KATP channel activity are MgATP and MgADP.
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At 5 mM glucose, KATP conductance is 7% of maximal and falls to 3% of maximal when glucose is increased to 10 mM.
“At 5 mM glucose, the conductance is 7% of maximal and this falls to 3% of maximal when glucose is increased to 10 mM (674).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [674]
In β-cells permeabilized with α-toxin, the IC50 for MgATP is 156 μM and channel activity is 16% of maximal at 1 mM MgATP.
“Similarly, it is lower in β-cells in which the plasma membrane has been permeabilized with α-toxin (Figure 3C): under these conditions, the IC50 is 156 µM and channel activity is 16% of maximal at 1 mM MgATP (674).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [674]
Measurements of channel activity in cell-attached patches before and after permeabilization with α-toxin, followed by dialysis with different ATP concentrations, yield submembrane ATP values of ~1 mM in glucose-free solution and ~3 mM in 11 mM glucose.
“However, measurements of channel activity in cell-attached patches before and after permeabilization of the plasma membrane with α-toxin, followed by dialysis with different ATP concentrations, yield values of ~1 mM in glucose-free solution and ~3 mM in 11 mM glucose (674).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [674]
The KATP current of dispersed β-cells is not fully inhibited until glucose reaches ~20 mM.
“Similarly, the KATP current of dispersed β-cells is not fully inhibited until glucose reaches ~20 mM (212, 674) (Figure 2C).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [674]
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Cites
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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Research works printed but not linked: 1
- Zingman LV, Alekseev AE, Bienengraeber M, Hodgson D, Karger AB, Dzeja PP, Terzic A: Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive Kϩ conductance. Neuron 31:233-245, 2001
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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-citationRegulation of ATP production by mitochondrial Ca2+
Tarasov, A. I., Griffiths, E. J., & Rutter, G. A. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.03.003 · Cited by 319 · see citing works
Self-citationModeling the pancreatic α-cell: dual mechanisms of glucose suppression of glucagon secretion
Watts, M., & Sherman, A. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.11.4504 · Cited by 45 · see citing works
- Authors
- Tarasov, A. I., Girard, C. A. J., & Ashcroft, F. M.
- Affiliations
- University of Oxford (GB)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-09-01
- Volume
- 55
- Issue
- 9
- Pages
- 2446-2454
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2166666951
- Cited by
- 68
- References
- 1
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 9 · 2013: 8 · 2012: 4
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Wellcome Trust
- Royal Society
- 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 › ATP Synthase and ATPases Research
- Keywords
- ATP-sensitive potassium channels, ATP sensitivity, pancreatic beta cells, MgATP, MgADP, nucleotide-binding domain, alpha-toxin permeabilization, inside-out patch
- MeSH terms
- Kcnj11 Channel, Acyl Coenzyme A, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Bacterial Toxins, Cell Membrane Permeability, Glucose, Hemolysin Proteins, Receptors, Drug, Potassium Channels, Patch-Clamp Techniques, ATP-Binding Cassette Transporters, Phosphatidylinositol 4,5-Diphosphate, Potassium Channels, Inwardly Rectifying, Insulin-Secreting Cells, Mice, Sulfonylurea Receptors
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