DEPOLARIZING ACTION OF A RED-TIDE DINOFLAGELLATE BREVETOXIN ON AXONAL MEMBRANES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (2) , 615-621
Abstract
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 .mu.M tetrodotoxin or 1 mM Na external solution. Pretreatment with tetrodotoxin completely antagonized the T17 depolarizing action. Upon washing the axon with the normal external solution, depolarization occurred. Pretreatment with 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 Na current only. The activation voltage for Na current was shifted in the hyperpolarizing direction by > 35 mV. T17 toxin also greatly depressed the fast inactivation of Na current. There was no significant change in the kinetics of the Na tail current. T17 toxin depolarized the membrane by selectively opening Na channels at fairly negative potentials and by inhibiting the fast Na inactivation. The binding site for T17 toxin was probably different from those for tetrodotoxin and sea anemone toxin.