Protein phosphorylation is required for diazoxide to open ATP-sensitive potassium channels in insulin (RINm5F) secreting cells.
The patch-clamp open-cell recording configuration has been used to investigate the effects of non-hydrolyzable analogues of ATP on the diazoxide-activation of KATP channels in the insulin-secreting cell line RINm5F. K+ channels inhibited by 0.1, 0.5 and 1.0 mM ATP were consistently activated by 200 microM diazoxide. During sustained activation of channels, exchange of ATP for either AMP-PNP, AMP-PCP or ATP gamma S abolished the effects of diazoxide. If diazoxide was added to the membrane in the continued presence of AMP-PNP, AMP-PCP or ATP gamma S either no effects were observed or alternatively a small transient activation of channels occurred. This study suggests that protein phosphorylation is necessary for diazoxide to activate ATP-sensitive potassium channels in insulin-secreting cells.
Dunne
M J
MJ
Department of Physiology, University of Liverpool, England.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007328:Insulin; D015221:Potassium Channels; D011506:Proteins; D000255:Adenosine Triphosphate; D003981:Diazoxide