Potential-dependent action of Anemonia sulcata toxins III and IV on sodium channels in crayfish giant axons.

Effects of toxins III and IV (ATX III and IV) from the sea anemone Anemonia sulcata on the Na current of crayfish giant axons were studied. Both toxins slowed the inactivation of Na channels, producing a maintained Na current during a depolarizing voltage pulse. Using the intensity of the toxin-induced maintained current as an index for the fraction of Na channels to which toxin is bound, the toxin association and dissociation kinetics were analyzed. The dissociation rate of ATX III was increased by two orders of magnitudes by depolarizing the membrane from -70 to -40 mV. This increase of the dissociation rate caused a marked decrease in the binding rate of ATX III to Na channels in the same potential range. ATX IV exhibited association and dissociation kinetics that had a potential dependency quite similar to that of ATX III in spite of different ionic charge distribution in these two toxins. The results support the view that the potential-dependent kinetics of these toxins are not due to an electrostatic interaction between the ionic charges of toxins and the membrane potential but result from a modulation of the binding energy depending on the gate configuration of the Na channel.