Characterisation of sulphonylurea and ATP-regulated K+ channels in rat pancreatic A-cells
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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Depolarization by tolbutamide-induced closure of KATP channels increases electrical activity, [Ca2+]i, exocytosis, and secretion in rat alpha-cells.
“Depolarization by tolbutamideinduced closure of the K ATP channels thus increases the electrical activity (24), [Ca 2ϩ ] i (8), exocytosis (28), and secretion (8) in rat ␣-cells”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [24]
Rat alpha-cells have a high density of KATP channels exceeding that in rat beta-cells.
“rat ␣-cells have a high density of K ATP channels, exceeding that in rat -cells (24)”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [24]
Glucose increases electrical activity and [Ca2+]i of rat alpha-cells.
“whereas glucose increases the electrical activity and [Ca 2ϩ ] i of rat ␣-cells (24)”
From Paradoxical Stimulation of Glucagon Secretion by High Glucose Concentrations (2006) · cites this paper as [24]
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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
- Licence
- 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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