Cited by 132Ion channel regulation and functionPancreatic function and diabetesAdenosine and Purinergic Signaling

Characterisation of sulphonylurea and ATP-regulated K+ channels in rat pancreatic A-cells

Bokvist, K., Olsen, H.L., Høy, M., Gotfredsen, C.F., Holmes, W.F., Buschard, K., Rorsman, P., Gromada, J.·1999·Pflügers Archiv

Abstract

We have monitored whole-cell and single channel ATP-sensitive K+ (KATP) currents in isolated rat glucagon-secreting pancreatic A-cells. Tolbutamide produced a concentration-dependent decrease in the whole-cell KATP conductance (Ki = 6 microM) and initiated action potential firing. The K+ channel opener diazoxide, but not cromakalim or pinacidil, inhibited electrical activity and increased the whole-cell K+ conductance fourfold. ATP applied to the intracellular face of the membrane inhibited KATP channel activity with a Ki of 17 microM, an effect that could be counteracted by Mg-ADP and Mg-GDP. GTP and UTP did not affect KATP channel activity. Phosphatidylinositol 4,5-bisphosphate activated KATP channels inhibited by ATP after a delay of 90 s. In situ hybridisation demonstrated the expression of the mRNA encoding KATP channel subunits Kir6.2 and SUR1 but not Kir6.1 and SUR2. We conclude that rat pancreatic A-cells express KATP channels with the nucleotide-, sulphonylurea- and K+ channel-opener sensitivities expected for a channel formed by Kir6.2 and SUR1 subunits.

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Crossref · 10.1007/s004249900076

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Authors
Bokvist, K., Olsen, H. L., Høy, M., Gotfredsen, C. F., Holmes, W. F., Buschard, K., Rorsman, P., & Gromada, J.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Copenhagen Municipal Hospital (DK)
  • Lund University (SE)
Venue
Pflügers Archiv
Published
1999-09
Volume
438
Issue
4
Pages
428-436
ISSN
  • 0031-6768 (ISSN-L)
  • 1432-2013
OpenAlex
W1999722905
Cited by
132
References
34
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 7
FWCI
2.18
Type
journal article
Language
en
Open access
closed
Locations
  • Pflügers Archiv - European Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
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, pancreatic A cells, glucagon secretion, Kir6.2, SUR1, tolbutamide, diazoxide, ATP inhibition, phosphatidylinositol 4,5-bisphosphate, Kir6.1, rats
MeSH terms
Adenosine Diphosphate, Adenosine Triphosphate, Animals, Electrophysiology, Guanosine Diphosphate, Guanosine Triphosphate, Hypoglycemic Agents, Islets of Langerhans, Male, Membrane Potentials, Rats, Inbred Lew, Receptors, Drug, Sulfonylurea Compounds, Tolbutamide, Uridine Triphosphate, Potassium Channels, ATP-Binding Cassette Transporters, Phosphatidylinositol 4,5-Diphosphate, Potassium Channels, Inwardly Rectifying, Potassium Channel Blockers, Rats, Sulfonylurea Receptors

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