Uncoupling of Cholinergic Synaptic Vesicles by the Presynaptic Toxin β‐Bungarotoxin

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Abstract
The effect of the presynaptic neurotoxin β‐bungarotoxin (β‐BuTx) on the acetylcholine (ACh) storage system of synaptic vesicles isolated from the electric organ of Torpedo californica was studied. The toxin can totally inhibit active transport of [3H]ACh by the vesicles in a Ca2+‐, time‐, and concentration‐dependent manner. Correlated with these effects is a 50–60% stimulation of the vesicle proton‐pumping ATPase activity. The β‐BuTx‐mediated transport inhibition and ATPase stimulation are antagonized by delipidated bovine serum albumin, not reversed by excess EGTA, and not mimicked by other cationic proteins or soybean or pancreatic trypsin inhibitors. The behavior is consistent with phospholipase A2 (PLA2)‐dependent damage to the vesicle membrane caused by β‐BuTx, which results in uncoupling of the ATPase and ACh transporter systems.The nonneurotoxic Naja naja venom PLA2 causes similar effects, except that it is slightly more potent on a molar basis. About 100‐fold more β‐BuTx is required to effect lysis of synaptic vesicles than to uncouple them. ATP is a strong inhibitor of β‐BuTx‐ but not of N. naja PLA2‐mediated uncoupling. The observations suggest that a component of β‐BuTx toxicity in the cholinergic terminal might involve attack on synaptic vesicles or vesicle‐like structures and that a nucleotide‐like factor might modulate the toxicity.