Effects of sulphonylureas on the volume-sensitive anion channel in rat pancreatic beta-cells.
1. The volume-sensitive anion conductance in rat pancreatic beta-cells was studied directly using the conventional whole-cell and perforated patch recording techniques, and indirectly by measuring 3H-taurine efflux from pre-loaded, perifused islets. 2. Using the conventional whole-cell recording configuration, activation of the outwardly-rectifying, DIDS-sensitive conductance was induced by glibenclamide (10 microM) but not by tolbutamide (100 microM) nor by meglitinide (20 microM). A high concentration of glibenclamide (100 microM) caused a voltage-and time-dependent inhibition of the conductance. Tolbutamide had a modest inhibitory effect on swelling-induced inward currents. 3. 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. 4. The rate of efflux of 3H-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. 5. Electrical activity of beta-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. 6. It is concluded that activity of the volume-sensitive anion conductance in rat pancreatic beta-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.
Best
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L
Department of Medicine, University of Manchester.
Benington
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S
D000818:Animals; D000838:Anions / Q000493:pharmacokinetics*; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013654:Taurine / Q000493:pharmacokinetics; D014044:Tolbutamide / Q000494:pharmacology
D000838:Anions; D001549:Benzamides; D007004:Hypoglycemic Agents; D007473:Ion Channels; D013453:Sulfonylurea Compounds; D013654:Taurine; C030516:meglitinide; D014044:Tolbutamide; D005905:Glyburide