Inhibition of neuronal acetylcholine sensitivity by α-toxins from Bungarus multicinctus venom

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Abstract
B. multicinctus venom contains several .alpha.-toxins besides the widely used .alpha.-bungarotoxin (Bgt 2.2). Two of the .alpha.-toxins (Bgt 3.1 and 3.3) inhibit neuronal acetylcholine (AcC) sensitivity when tested on [chicken] ciliary ganglion neurons in cell culture. Over 90% of the AcC sensitivity recorded in response to iontophoretic application of AcC was blocked when the neurons were incubated with either toxin at 10-7 M for 1 h at 37.degree. C. The blockade could be partially reversed by incubating the neurons for 1-2 h in medium lacking the toxins. The neurons also had a high-affinity binding site for Bgt 2.2, as indicated by binding studies with rhodamine-labeled Bgt 2.2. Concentrations of Bgt 2.2 (10-7 M) that should be nearly adequate to saturate the high-affinity site had no detectable effect on AcC sensitivity of the neurons. Higher concentrations of Bgt 2.2 (10-5 M) produced a partial inhibition of AcC sensitivity, suggesting that the neurons had 2 classes of binding sites for Bgt 2.2 (with the low-affinity site affecting AcC sensitivity) or that the preparation of Bgt 2.2 contained minor components (e.g., Bgt 3.1 or 3.3) that were responsible for the blockade. The mechanisms by which Bgt 3.1 and 3.3 inhibit neuronal AcC sensitivity remain unknown. If they bind specifically to the AcC receptor, they will be useful agents for studying the distribution and regulation of this membrane component.