Calcium‐Dependent and ‐Independent Acetylcholine Release from Electric Organ Synaptosomes by Pardaxin: Evidence of a Biphasic Action of an Excitatory Neurotoxin

Mònica Arribas, Joan Blasi, Philip Lazarovici, Jordi Marsal*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Abstract: 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 × 10−7M), 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 × 10−7M to 10−5M, 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 10−6M pardaxin‐treated synaptosomes revealed nerve terminals depleted of synaptic vesicles and containing cisternae. At higher toxin concentrations ( 10−5M), 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.

Original languageEnglish
Pages (from-to)552-558
Number of pages7
JournalJournal of Neurochemistry
Volume60
Issue number2
DOIs
StatePublished - Feb 1993

Keywords

  • Acetylcholine release
  • Cholinergic synaptosomes
  • Excitatory neurotoxin
  • Pardaxin
  • Pore‐forming

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