Abstract
The action of polymyxin B (0.1 μM) 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 μM 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).
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Harding, E.A., Jaggar, J.H., Squires, P.E. et al. Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells. Pflugers Arch. 426, 31–39 (1994). https://doi.org/10.1007/BF00374667
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DOI: https://doi.org/10.1007/BF00374667