ISSN:
1432-2013
Keywords:
ATP-sensitive K+ channel
;
Insulin-secreting cell
;
Patch-clamp
;
Polymyxin B
;
Protein kinase C
;
RINm5F cells
;
Phorbol ester
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00374667
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