The effects of alpha-latrotoxin of black widow spider venom on synaptosome ultrastructure. A morphometric analysis correlating its effects on transmitter release.
The morphological effects of alpha-latrotoxin, the major component of black widow spider venom, were studied quantitatively in a crude synaptosome fraction (prepared from rat brain cortices) which was incubated at 37 degrees C for 10 min in Ringer solutions. Two toxin concentrations were employed, one causing a very large stimulation of transmitter release (approximately 65% and approximately 43% release of [3H]noradrenaline from preloaded synaptosomes, with and without Ca2+ in the incubation buffer), the other 50-60% as active. Incubated synaptosomes, fixed in suspension with aldehydes, were evenly dispersed in agarose before embedding, to assure randomized sampling in the subsequent morphometric analysis. In all the experimental conditions investigated, alpha-latrotoxin treatment caused a significant decrease in the density (number/unit area) of synaptic vesicles in synaptosome profiles. Such an effect was dose-dependent and partially Ca2+-dependent, in good agreement with the data on transmitter release. At high toxin concentration a moderate increase of synaptosome volume and surface area was observed, both with and without Ca2+. Mitochondrial swelling appeared only in synaptosomes treated in Ca2+ containing medium. These effects of alpha-latrotoxin are similar to those described previously at the neuromuscular junction. Thus, the toxin might be a tool of general use for studying vertebrate synapses.
D000818:Animals; D001180:Arthropod Venoms / Q000032:analysis* / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000648:ultrastructure; D005260:Female; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013111:Spider Venoms / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014316:Tritium
D001180:Arthropod Venoms; D013111:Spider Venoms; D014316:Tritium; C020763:alpha-latrotoxin; D009638:Norepinephrine