Effects of cicutoxin and related polyacetylenes from Cicuta virosa on neuronal action potentials: A comparative study on the mechanism of the convulsive action

Cicutoxin, the convulsant principle of water hemlock, Cicuta virosa L., and the related polyacetylenes isocicutoxin, cicudiol, cicutol, falcarindiol, and falcarinol(20-100 mu mol/l) were investigated concerning their influence on electrophysiological parameters using the giant cell RPD1 of the right parietal ganglion of the pond snail, Lymnaea stagnalis L., as a model neurone. Action potentials occurring spontaneously in this cell were recorded by the intracellular microelectrode technique. The duration of depolarisation, the duration of repolarisation, and the amplitude of the action potentials were determined before and after addition of test substances. Cicutoxin increased the duration of repolarisation dose-dependently up to sixfold at 100 mu mol/l. Isocicutoxin caused a prolongation of the repolarisation phase up to twofold at 60 mu mol/l, but its effect was reduced at 100 mu mol/l. The other polyacetylenes tested did not show any effects on the parameters measured. It is concluded that a molecule with two hydroxy groups separated by a rigid hydrocarbon chain of a certain length is required for the described action. The action potential prolongation provoked by cicutoxin could be responsible for the toxicity of the substance in vertebrates.