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.
Department of Physiology, University of Tübingen, Germany.
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Krippeit-Drews
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Zempel
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Ammon
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Lang
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Drews
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D017136:Ion Transport / Q000187:drug effects; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D001391:Azo Compounds; D015220:Calcium Channels; D007328:Insulin; D015221:Potassium Channels; D013439:Sulfhydryl Reagents; C013475:diazenedicarboxylic acid bis(N'-methylpiperazide)