Effects of sulphonylureas on the volume‐sensitive anion channel in rat pancreatic β‐cells
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The volume‐sensitive anion conductance in rat pancreatic β‐cells was studied directly using the conventional whole‐cell and perforated patch recording techniques, and indirectly by measuring 3 H‐taurine efflux from pre‐loaded, perifused islets. Using the conventional whole‐cell recording configuration, activation of the outwardly‐rectifying, DIDS‐sensitive conductance was induced by glibenclamide (10 μ M) but not by tolbutamide (100 μ M) nor by meglitinide (20 μ M). A high concentration of glibenclamide (100 μ M) caused a voltage‐and time‐dependent inhibition of the conductance. Tolbutamide had a modest inhibitory effect on swelling‐induced inward currents. In perforated patch recordings, glibenclamide, tolbutamide and meglitinide were all without effect on the conductance, although activation could be induced under these conditions by exposure to a hypotonic bath solution. The rate of efflux of 3 H‐taurine, a marker for activity of the volume‐sensitive anion channel, from preloaded, perifused islets was markedly stimulated by exposure to a hypotonic solution. However, glibenclamide and tolbutamide were both without effect. Electrical activity of β‐cells in response to glibenclamide or tolbutamide was not inhibited by 4,4′‐dithiocyanatostilbene‐2,2′‐disulphonic acid (DIDS), an inhibitor of the volume‐sensitive anion channel. It is concluded that activity of the volume‐sensitive anion conductance in rat pancreatic β‐cells is not modulated by the sulphonylurea receptor. The activation of the conductance by glibenclamide in whole‐cell recordings could be the result of a non‐specific interaction of the drug with plasma membrane lipids. British Journal of Pharmacology (1998) 125, 874–878; doi:10.1038/sj.bjp.0702148
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There is evidence that glucose may activate the volume-regulated anion (VRAC) Cl- channel, and VRAC was recently identified as LRRC8A, which is expressed at low but detectable levels in both mouse and human β-cells.
“There is evidence that glucose may activate the volume-regulated anion (VRAC) Cl- channel (65, 349). VRAC was recently identified as the ‘leucine-rich repeats containing 8A’ protein (Lrrc8a/LRRC8A) (527, 713), which is expressed at low but detectable levels in both mouse and human β-cells (3, 68, 146, 475).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [65]
The citation is attached to the claim that glucose may activate the volume-sensitive anion channel. The Introduction describes activation by cell swelling, and the Discussion examines glibenclamide, but a search for glucose found no passage addressing glucose-induced activation. The later LRRC8A and expression claims have separate citations. (LLM, conf=0.73)
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Research works printed but not linked: 2
- Bailey, C.J. & Flatt, P.R. pp. 93 ± 106. London: Smith-Gordon.
- OKADA, Y. (1997). Volume expansion-sensing outward-recti®er Cl 7 channel: fresh start to the molecular identity and volume sensor. American Journal of Physiology 273, C755 ± C789.
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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
- Authors
- Best, L., & Benington, S.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Best, L
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1998-10
- Volume
- 125
- Issue
- 4
- Pages
- 874-878
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1571040
- OpenAlex
- W2168031703
- Cited by
- 18
- References
- 0
- Citations by year
- 2023: 1 · 2019: 1 · 2017: 1 · 2014: 2 · 2013: 1
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- sulfonylureas, pancreatic beta cells, glibenclamide, tolbutamide, meglitinides, taurine efflux, cell swelling, sulfonylurea receptor, beta-cell electrical activity, plasma membrane lipids
- MeSH terms
- Animals, Anions, Benzamides, Cells, Cultured, Dose-Response Relationship, Drug, Evoked Potentials, Glyburide, Hypoglycemic Agents, Ion Channels, Islets of Langerhans, Sulfonylurea Compounds, Taurine, Tolbutamide, Ion Transport, Rats
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