Cytosolic ADP enhances the sensitivity to tolbutamide of ATP-dependent K +channels from pancreatic B-cells

The effects of intracellular purine nucleotides on tolbutamide-induced block of ATP-dependent K +channels from mouse pancreatic B-cells were studied using the patch-clamp technique. When applied to the inside of excised patches tolbutamide alone blocked channel activity half-maximally at 55μM and the concentration-response curve for the inhibition of K +channels by tolbutamide was flat. ADP (1 mM), but not other nucleotides (AMP, GTP or GDP) increased the steepness of the concentration-response curve and decreased the half-maximally effective tolbutamide concentration to 4.2 μM. It is suggested that the ATP-dependent K +channel or a closely related structure contains a receptor which is accessible for cytosolic ADP and controls the sensitivity to tolbutamide.