Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca2+-activated K+ channels

Imlach, Wendy L., Finch, Sarah C., Zhang, Yanli, Dunlop, James and Dalziel, Julie E. (2011) Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca2+-activated K+ channels. Toxicon, 57 5: 686-694. doi:10.1016/j.toxicon.2011.01.013


Author Imlach, Wendy L.
Finch, Sarah C.
Zhang, Yanli
Dunlop, James
Dalziel, Julie E.
Title Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca2+-activated K+ channels
Journal name Toxicon   Check publisher's open access policy
ISSN 0041-0101
1879-3150
Publication date 2011-04
Sub-type Article (original research)
DOI 10.1016/j.toxicon.2011.01.013
Volume 57
Issue 5
Start page 686
End page 694
Total pages 9
Place of publication Oxford, England, U.K.
Publisher Pergamon
Collection year 2012
Language eng
Formatted abstract
The aim of this study was to compare the mode of action of the commonly used BK inhibitor paxilline with that of the more recently discovered lolitrem B. Similarities and differences in characteristics of inhibition between the two compounds were investigated. We have previously shown that lolitrem B does not affect the BK channel G–V, in contrast to the rightward shift produced by paxilline. These different effects on the voltage-dependence of activation suggest different modes of action for these two compounds. In this study we show that inhibition by both paxilline and lolitrem B is characterized by an open state preference for BK (hSlo) channels. Both compounds had a 3-fold higher apparent affinity under conditions likely to favour the open state, suggesting they have a similar BK conformational preference for binding. Furthermore, both compounds had a calcium concentration-dependence to their inhibitory effects. The G–V shift induced by paxilline was calcium concentration-dependent.
Keyword Large conductance calcium-activated
Potassium Channels
BK ion channel
Patch-clamp
Paxilline
Lolitrem
BK channel inhibitor
Fungal toxin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Received 29 November 2010. Revised 22 January 2011. Accepted 24 January 2011. Available online 5 February 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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