EFFECTS OF MEMBRANE PERMEANT AND IMPERMEANT THIOL REAGENTS ON CA2+ AND K+ CHANNEL CURRENTS OF MOUSE PANCREATIC B-CELLS

The membrane permeant thiol reagent diazene dicarboxylic acid bis-(N'-methylpiperazide) (DIP) has been shown to inhibit insulin secretion and Ca2+ uptake in pancreatic B cells in the presence of a stimulating glucose concentration (20 mM), whereas the nonpenetrating analog of DIP (bis-N'-methyliodide; DIP+2) stimulates insulin release and Ca2+ uptake at a low glucose concentration (3 mM). The effects of DIP and DIP+2 were tested on currents through ATP-sensitive K+(K-ATP(+)) channels and voltage-dependent Ca2+ channels (with Ba2+ as the charge carrier) in mouse pancreatic B cells in the whole-cell mode of the patch-clamp technique. DIP (0.1 mM) almost completely inhibited both the K-ATP(+) and Ca2+ channel currents. In contrast, DIP+2 (0.1 mM)) did not affect the Ca2+ channel current but reduced the whole-cell K-ATP(+) current by about 40%. The data strongly suggest that the suppression of insulin secretion previously observed with DIP is due to a reduction of the current through voltage-dependent Ca2+ channels, whereas the stimulation of hormone release induced by DIP+2 is caused by the partial inhibition of K-ATP(+) channel current.