Cited by 39Ion channel regulation and functionPancreatic function and diabetesAdenosine and Purinergic Signaling

The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells

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Ashcroft, F.M., Kakei, M., Gibson, J.S., Gray, D.W., Sutton, R.·1989·Diabetologia

Abstract

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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Authors
Ashcroft, F. M., Kakei, M., Gibson, J. S., Gray, D. W., & Sutton, R.
Affiliations
John Radcliffe Hospital (GB)
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
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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