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

Wendy L. Imlach, Sarah C. Finch, Yanli Zhang-James, James S Dunlop, Julie E. Dalziel

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)686-694
Number of pages9
JournalToxicon : official journal of the International Society on Toxinology
Volume57
Issue number5
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

Keywords

  • BK channel inhibitor
  • BK ion channel
  • Fungal toxin
  • Large conductance calcium-activated potassium channel
  • Lolitrem
  • Patch-clamp
  • Paxilline

Cite this