Ciguatoxin is a novel type of Na+ channel toxin

Purified ciguatoxin at 0.1 to 10 ng/ml inhibits the net accumulation of neurotransmitters (gamma-aminobutyric acid and dopamine) by brain synaptosomes. This action is due to a stimulation of neurotransmitter release. The half-maximum effect of the toxin is observed at 0.62 ng/ml. The effect of ciguatoxin is completely inhibited by tetrodotoxin (K0.5 = 4 nM). Electrophysiological studies on neuroblastoma cells indicate that ciguatoxin induces a membrane depolarization which is prevented by tetrodotoxin and which is due to an action that increases Na+ permeability. Under appropriate conditions ciguatoxin creates spontaneous oscillations in the membrane polarization level and repeated action potentials. Ciguatoxin stimulates 22Na+ entry through the voltage-dependent Na+ channels of neuroblastoma cells and rat skeletal myoblasts when it is used in synergy with veratridine, batrachotoxin, pyrethroids, sea anemone, or scorpion toxins. The half-maximum effect of ciguatoxin on 22Na+ flux in the presence of veratridine occurs at a concentration of 0.5 ng/ml. Stimulation of 22Na+ flux by ciguatoxin is abolished by tetrodotoxin. These results taken together indicate that ciguatoxin belongs to a new class of toxins acting on Na+ channels.