Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells.
The action of polymyxin B (0.1 microM) on ATP-sensitive K+ (K+ATP) channels in RINm5F insulin-secreting cells was investigated by patch-clamp techniques. Using inside-out patches, open-cells and outside-out patches, polymyxin B was found to block K+ATP channels by, on average, approximately 90-95% of the initial control level of channel activity. The effects were rapid in onset, sustained and readily reversible. Similar effects were found in patches excised from cells pretreated overnight with 1 microM of the phorbol ester phorbol myristate acetate (PMA). External block of channels was associated with a marked decrease in single-channel current amplitude, whereas these effects were not seen when polymyxin B was added to the inside face of the membrane. In patches bathed with internally applied ATP (0.5 mM) and ADP (0.5 mM), polymyxin B inhibited channels but its actions were not reversible upon removal of the compound. However, when the same protocol was undertaken upon cells pre-treated with PMA, the effects of polymyxin B were readily reversed. Our data suggests that polymyxin B is a novel modulator of K+ATP channels, exhibiting multiple blocking actions that may possibly involve a direct effect upon the channel and indirect effects mediated through the inhibition of endogenous protein kinase(s).
Harding
E A
EA
Department of Biomedical Science, The University, Western Bank, Sheffield, UK.
Jaggar
J H
JH
Squires
P E
PE
Dunne
M J
MJ
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011112:Polymyxin B / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats
D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011112:Polymyxin B