EFFECTS OF SULFONYLUREAS ON THE VOLUME-SENSITIVE ANION CHANNEL IN RATPANCREATIC 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 H-3-taurine ef flux 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 mu M) but not by tolbutamide (100 mu M) nor by meglitinide (20 mu M). A high co ncentration of glibenclamide (100 mu M) caused a voltage-and time-depe ndent inhibition of the conductance. Tolbutamide had a modest inhibito ry effect on swelling-induced inward currents. 3 In perforated patch r ecordings, 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 H-3-taurine, a marker for activity of the volume-sensiti ve anion channel, from preloaded, perifused islets was markedly stimul ated by exposure to a hypotonic solution. However, glibenclamide and t olbutamide were both without effect. 5 Electrical activity of beta-cel ls 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 o f 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 res ult of a non-specific interaction of the drug with plasma membrane lip ids.