Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells

Elizabeth A. Harding, Jonathan Jaggar, Paul E. Squires, Mark J. Dunne

Research output: Contribution to journalArticle

16 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalPflügers Archiv European Journal of Physiology
Volume426
Issue number1-2
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Polymyxin B
KATP Channels
Insulin-Secreting Cells
Insulin
Adenosine Triphosphate
Tetradecanoylphorbol Acetate
Level control
Clamping devices
Phorbol Esters
Patch-Clamp Techniques
Adenosine Diphosphate
Protein Kinases
Modulators
Membranes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells. / Harding, Elizabeth A.; Jaggar, Jonathan; Squires, Paul E.; Dunne, Mark J.

In: Pflügers Archiv European Journal of Physiology, Vol. 426, No. 1-2, 01.01.1994, p. 31-39.

Research output: Contribution to journalArticle

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