Depolarizing action of a red-tide dinoflagellate brevetoxin on axonal membranes.
The neurotoxic actions of T17 , a toxin isolated from the red-tide dinoflagellate Ptychodiscus brevis, on membrane excitability were investigated by the intracellular microelectrode technique on the crayfish giant axons and by the voltage clamp experiments on the squid giant axons. External application of T17 toxin caused a concentration-dependent depolarization, transient repetitive discharges, followed by depression of the action potential leading to a complete block of excitability. The reversibility of the depolarizing action upon washing decreased as the time of toxin treatment was increased. The T17 -induced depolarization was effectively reversed by 0.3 microM tetrodotoxin or 1 mM Na external solution. Pretreatment with tetrodotoxin completely antagonized the T17 depolarizing action. However, upon washing the axon with the normal external solution, depolarization occurred. Pretreatment with either procaine or dibucaine at high doses also offered protection against the depolarization. The toxin action was greatly potentiated by the sea anemone toxin, anthopleurin-A. The voltage clamp experiments showed that T17 toxin affected sodium current only. The activation voltage for sodium current was shifted in the hyperpolarizing direction by more than 35 mV. T17 toxin also greatly depressed the fast inactivation of sodium current. However, there was no significant change in the kinetics of the sodium tail current. These results indicate that T17 toxin depolarizes the membrane by selectively opening sodium channels at fairly negative potentials and by inhibiting the fast sodium inactivation. We also infer that the binding site for T17 toxin is different from those for tetrodotoxin and sea anemone toxin.
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects*; D001665:Binding Sites; D004141:Dinoflagellida / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000187:drug effects; D008387:Marine Toxins / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D035964:Oxocins; D010455:Peptides / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D000095702:Polyether Toxins
D000779:Anesthetics, Local; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D008387:Marine Toxins; D035964:Oxocins; D010455:Peptides; D012964:Sodium; D013779:Tetrodotoxin; C012746:anthopleurin-A; C041017:brevetoxin T17; D000095702:Polyether Toxins