Botulinum toxin A blocks glutamate exocytosis from guinea-pig cerebral cortical synaptosomes

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Abstract
1. 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°C for 1–2 h. 2. The toxin has no effect on synaptosomal respiratory control, respiratory capacity, ATP synthesis, plasma‐membrane 86Rb+ permeability or plasma‐membrane potentical, does not inhibit the entry of 45Ca2+ into the synaptosome upon depolarization and does not alter the ability of intrasynaptosomal mitochondria to sequester Ca2+. 3. 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. 4. 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.