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.
Dalziel
Julie E
JE
AgResearch Limited, Biomembrane Group, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North 5301, New Zealand. julie.dalziel@agresearch.co.nz
Finch
Sarah C
SC
Dunlop
James
J
D002478:Cells, Cultured; D006801:Humans; D026121:Indole Alkaloids; D020128:Inhibitory Concentration 50; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects; D009183:Mycotoxins / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000502:physiology; D014162:Transfection
D026121:Indole Alkaloids; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009183:Mycotoxins; D009498:Neurotoxins; D024681:Potassium Channels, Calcium-Activated; C033673:lolitrem B