Actions of Ptychodiscus brevis toxins on nerve and muscle membranes.
Pharmacological actions of two brevetoxins isolated from Ptychodiscus brevis, T17 and T34, on nerve and muscle membranes were studied using vertebrate and invertebrate preparations. T17 (10 ng/ml) caused an increase in the frequency of miniature endplate potentials (MEPPs) in rat and frog neuromuscular junctions. Application of tetrodotoxin (TTX) completely abolished the increase in MEPP frequency. The results suggest that T17 depolarizes the nerve terminal through opening of the sodium channel. Application of either T17 or T34 to the crayfish and squid giant axons caused a dose-dependent depolarization of the axon membranes with a maximum depolarization of about 30 mV. The depolarizing action was antagonized by sodium-free external saline solution or TTX. Voltage clamp experiments demonstrated that the primary action of the toxins is to cause the sodium channels to open at the normal resting potential. The binding of toxin to a channel site could be prevented by procaine, but not by TTX. The binding site for T17 is presumably separate from the TTX receptor, but related or identical to the binding site for procaine. The brevetoxin-induced depolarization of the nerve terminal membrane with the subsequent enhanced transmitter release is the underlying mechanism for a number of pharmacological actions on various neuro-effector systems.
C H
CH
Wu
J M
JM
Huang
S M
SM
Vogel
V S
VS
Luke
W D
WD
Atchison
T
T
Narahashi
D000818:Animals; D003400:Astacoidea; D003386:Brachyura; D049832:Decapodiformes; D004141:Dinoflagellida; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008566:Membranes / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D011894:Rana pipiens; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
C017885:Gymnodinium breve toxin; D007473:Ion Channels; D008387:Marine Toxins; D013779:Tetrodotoxin