Botulinum toxin A blocks glutamate exocytosis from guinea-pig cerebral cortical synaptosomes.
The exocytotic release of L-glutamate from guinea-pig cerebral cortical synaptosomes can be extensively inhibited by preincubation with botulinum neurotoxin type A at 37 degrees C for 1-2 h. The toxin has no effect on synaptosomal respiratory control, respiratory capacity, ATP synthesis, plasma-membrane 86Rb+ permeability or plasma-membrane potential, does not inhibit the entry of 45Ca2+ into the synaptosome upon depolarization and does not alter the ability of intrasynaptosomal mitochondria to sequester Ca2+. The blockade of Ca2+-dependent glutamate release may be totally reversed by the Ca2+/2 H+-exchange ionophore ionomycin, but not by increasing extracellular Ca2+ concentration. It is suggested (a) that exocytosis is triggered by the penetration of Ca2+ into an intracellular hydrophobic milieu; (b) that this stage is blocked by the toxin and (c) that ionomycin is able to bypass this block and deliver Ca2+ to the exocytotic apparatus.
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D004987:Ethers / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D015759:Ionomycin; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism
D004987:Ethers; D005971:Glutamates; D007473:Ion Channels; D018698:Glutamic Acid; D015759:Ionomycin; D001905:Botulinum Toxins; D002118:Calcium