Relationship between the binding sites for an α-conotoxin and snake venom neurotoxins in the nicotinic acetylcholine receptor from Torpedo californica

Abstract

Photoinduced cross-links between the iodinated Lys26- p-azidobenzoyl derivative of neurotoxin II from Naja naja oxiana cobra venom and nicotinic acetylcholine receptor from Torpedo californica (AChR) have been studied in the presence of α-conotoxin GI from the marine snail C. geographus. Preincubation of the AChR-enriched membranes with increasing concentrations of α-conotoxin GI protects first the γ subunit from photo-labelling and then the δ subunit, the ic 50 values being 0.76 and 5.01 μM, respectively. The results obtained, in view of the relevant data in literature, demonstrate that the ( α + γ) site, which is the high affinity site for d-tubocurarine, has also a higher affinity for an α-conotoxin than the ( α + δ) containing site. The latter has a somewhat higher affinity than the ( α + γ) site towards some naturally occurring snake venom α-neurotoxins or their derivatives.