Calcium-dependent and -independent acetylcholine release from electric organ synaptosomes by pardaxin: evidence of a biphasic action of an excitatory neurotoxin

J Neurochem. 1993 Feb;60(2):552-8. doi: 10.1111/j.1471-4159.1993.tb03184.x.


The effect of pardaxin, a new excitatory neurotoxin, on neurotransmitter release was tested using purely cholinergic synaptosomes of Torpedo marmorata electric organ. Pardaxin elicited the release of acetylcholine with a biphasic dose dependency. At low concentrations (up to 3 x 10(-7) M), the release was calcium-dependent and synaptosomal structure was well preserved as revealed by electron microscopy and measurements of occluded lactate dehydrogenase activity. At concentrations from 3 x 10(-7) M to 10(-5) M, the pardaxin-induced release of acetylcholine was independent of extracellular calcium, and occluded synaptosomal lactate dehydrogenase activity was lowered, indicating a synaptosomal membrane perturbation. Electron microscopy of 10(-6) M pardaxin-treated synaptosomes revealed nerve terminals depleted of synaptic vesicles and containing cisternae. At higher toxin concentrations (> or = 10(-5) M), there were striking effects on synaptosomal morphology and occluded lactate dehydrogenase activity, suggesting a membrane lytic effect. We conclude that, at low concentrations, this neurotoxin is a promising tool to investigate calcium-dependent mechanisms of neurotransmitter release in the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Calcium / pharmacology*
  • Dose-Response Relationship, Drug
  • Electric Organ / drug effects
  • Electric Organ / metabolism*
  • Electric Organ / ultrastructure
  • Fish Venoms / pharmacology*
  • Flatfishes
  • Kinetics
  • L-Lactate Dehydrogenase / metabolism
  • Microscopy, Electron
  • Neurotoxins / pharmacology*
  • Potassium Chloride / pharmacology
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism*
  • Torpedo


  • Fish Venoms
  • Neurotoxins
  • Potassium Chloride
  • pardaxin
  • L-Lactate Dehydrogenase
  • Acetylcholine
  • Calcium