Effects du gambierol sur les canaux potassium et la libération de neurotransmetteurs. [Effects of gambierol on potassium channels and neurotransmitter release]

Gambierol is a marine polyether toxin isolated with ciguatoxins (CTXs) from cultures of the toxic dinoflagellate Gambierdiscus toxicus. It is toxic to mice, inducing symptoms resembling those of CTXs. This suggests that gambierol is involved in ciguatera, a worldwide-spread food poisoning caused by the consumption of fish contaminated with toxins produced by G. toxicus. We showed previously that CTXs interact preferentially with voltage-gated Na+ than K+ channels of excitable tissues. In contrast to CTXs, gambierol has been reported to be more efficient in blocking K+ than Na+ channels in gustative cells. In the present work, we report that gambierol, in the nanomolar range, inhibits voltage-dependent K+ channels in primary cultures of rat embryonic chromaffin cells, and greatly increases the evoked and delayed quantal acetylcholine (ACh) releases in isolated neuromuscular preparations ( frog cutaneaous pectoris and mouse phrenic-hemidiaphragm), without modifying the muscle resting potential. In contrasr, spontaneous quantal ACh release remains unaffected by sub-micromolar concentrations of gambierol. Our data suggest that nanomolar concentrations of gambierol block K+ channels in chromaffin cells, and modulate evoked and delayed quantal ACh releases at the neuromuscular junction, effects that greatly differ from those of CTXs. Gambierol is more active than 3,4-diaminopyridine, a well known K+ channel blocker.