Journal
TOXICOLOGY LETTERS
Volume 155, Issue 3, Pages 421-426Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2004.11.011
Keywords
BK channel; lolitrem; endophyte; indole diterpene; Neotyphodium lolii
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The effects of the mycotoxin lolitrem B on the function of hSlo large conductance calcium-activated potassium channels expressed in HEK293 cells have been investigated using inside-out membrane patches. Lolitrem B potently inhibited hSlo potassium currents activated by depolarising voltage pulses in the presence of 10 muM free calcium. At a concentration of 100 nM, lolitrem B rapidly and completely inhibited outward potassium currents. The concentration that produced half-maximal inhibition was 3.7 nM, indicating a high apparent affinity for hSlo channels. This is the first time that a molecular site of action has been identified for a compound of the lolitrem structural class of indole diterpene and identifies a novel BK channel blocker. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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