The fungal neurotoxin lolitrem B inhibits the function of human large conductance calcium-activated potassium channels.

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 microM 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.