The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells
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The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.
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The whole-cell KATP conductance in the absence of glucose in human β-cells is <10% of that found in mouse β-cells, being around 60 pS/pF, and this difference is likely due to a lower open probability.
“However, the whole-cell KATP conductance in the absence of glucose is <10% of that found in mouse β-cells, being around 60 pS/pF (535). As there is no major difference in single-channel conductance or channel density (28), the difference is likely to be due to a lower open probability.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [28]
The Discussion (page unavailable) reports very low initial whole-cell conductance in intact human β-cells, supporting the general point that few KATP channels are active. But it gives less than 50 pS per cell, not around 60 pS/pF; using the 7.6 pF mean capacitance reported in Whole-cell currents (page unavailable) yields less than about 7 pS/pF. The paper does not establish the claimed <10% comparison with mouse β-cells. The lower-open-probability explanation follows a separate citation in the citing sentence, so it is not assessed as an attribution to this paper. (LLM, conf=0.84)
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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-citation
- Authors
- Ashcroft, F. M., Kakei, M., Gibson, J. S., Gray, D. W., & Sutton, R.
- Affiliations
- John Radcliffe Hospital (GB)
- ORCID
- Ashcroft, F.M.
- Venue
- Diabetologia
- Published
- 1989-08
- Volume
- 32
- Issue
- 8
- Pages
- 591-8
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2116167295
- Cited by
- 39
- References
- 0
- Citations by year
- 2026: 1 · 2023: 1 · 2018: 3 · 2017: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- 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 › Physiology › Adenosine and Purinergic Signaling
- Keywords
- ATP-sensitive potassium channels, sulfonylurea receptor, tolbutamide, ATP inhibition, calcium-activated potassium channels, type 2 diabetes, insulin secretion
- MeSH terms
- Adenosine Triphosphate, Calcium, Humans, Islets of Langerhans, Kinetics, Membrane Potentials, Tolbutamide, Potassium Channels, In Vitro Techniques
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