A NOVEL K+ CHANNEL BLOCKER ISOLATED FROM HICCUP NUT TOXIN

COMBRETASTATIN B1, a polyhydroxybibenzyl compound extracted from the f ruit of Combretum kraussii, known to contain 'hiccup nut' toxin, rever sibly increased the duration, but not the peak or the rate of rise, of the action potential in rat sensory neurones by approximately 300%. T his effect was only seen when it was applied to the extracellular side of the membrane. No effects on the resting potential were observed. K + delayed rectifier currents were inhibited in neurones and in human m yotubes with an IC50 of about 300 mu M; the HERG-type inward rectifier channels in tumour cells were inhibited to a greater degree. Due to i ts selective action and the similarity of its blockade to that produce d by class III antiarrhythmic drugs, the toxin could be the origin of compounds of potentially significant pharmacological interest.