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. 1992 Sep;107(1):87–94. doi: 10.1111/j.1476-5381.1992.tb14467.x

Diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel in mouse pancreatic beta-cells.

C Schwanstecher 1, C Dickel 1, I Ebers 1, S Lins 1, B J Zünkler 1, U Panten 1
PMCID: PMC1907615  PMID: 1422580

Abstract

1. In mouse pancreatic beta-cells the regulation of the diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel (K-ATP-channel) was examined by use of the patch-clamp technique. 2. In intact beta-cells incubated at 37 degrees C in the presence of 3 mM D-glucose, diazoxide did not affect the single channel conductance but stimulated channel-opening activity. Diazoxide produced half-maximal effects at 82 microM and 13 fold activation at maximally effective concentrations (300-400 microM). The response to diazoxide (300 microM) was not completely suppressed by saturating tolbutamide concentrations (1 or 5 mM). 3. Inside-out patch-clamp experiments were carried out using an experimental protocol favouring phosphorylation of membrane proteins. Under these conditions diazoxide was ineffective in the absence of any nucleotides, weakly effective in the presence of MgATP (26 or 87 microM) and strongly effective in the presence of the Mg complexes of adenosine 5'-diphosphate, 2'-deoxyadenosine 5'-diphosphate or guanosine 5'-diphosphate (MgADP, MgdADP or MgGDP). 4. In inside-out patches exposed to nucleotide-free solutions, saturating concentrations of tolbutamide did not cause complete block of K-ATP-channels. When the channels were activated by MgdADP (48 microM), tolbutamide was even less effective. Sensitization of MgdADP-induced channel activation by diazoxide further weakened the effects of tolbutamide. 5. Diazoxide (50 or 300 microM) prevented the complete channel block induced by saturating tolbutamide concentrations in the presence of Mg2+ and ADP (1 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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