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Actions of Ptychodiscus brevis toxins on nerve and muscle membranes
Abstract:
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.
Insights
Brevetoxins T17 and T34 from Ptychodiscus brevis open sodium channels, causing nerve cell depolarization and increased neurotransmitter release. This mechanism underlies their diverse pharmacological effects on neuro-effector systems.
Area of Science:
- Neuroscience
- Marine Biology
- Pharmacology
Background:
- Brevetoxins are potent marine neurotoxins produced by Ptychodiscus brevis.
- These toxins are known to affect the nervous system, but their precise mechanisms of action require further elucidation.
Purpose of the Study:
- To investigate the pharmacological actions of brevetoxins T17 and T34 on nerve and muscle membranes.
- To determine the specific ion channels involved in brevetoxin-induced neurotoxicity.
Main Methods:
- Electrophysiological studies on vertebrate (rat, frog) and invertebrate (crayfish, squid) preparations.
- Experiments included measuring miniature endplate potentials (MEPPs) and performing voltage clamp analysis.
- Investigated the effects of tetrodotoxin (TTX) and sodium-free solutions on toxin-induced responses.
Main Results:
- Brevetoxin T17 increased MEPP frequency in neuromuscular junctions, an effect blocked by TTX, suggesting nerve terminal depolarization via sodium channel opening.
- Both T17 and T34 caused dose-dependent depolarization of giant axons, antagonized by TTX and sodium-free saline.
- Voltage clamp data indicated that brevetoxins open sodium channels at resting potential; the binding site is distinct from TTX but may overlap with procaine's site.
Conclusions:
- Brevetoxins T17 and T34 primarily act by opening voltage-gated sodium channels in nerve membranes.
- This toxin-induced depolarization leads to enhanced neurotransmitter release, explaining their broad pharmacological effects.