α-Conotoxin BuIA – Ion Channels and Transporters

α-Conotoxin BuIA has been identified within the venom of the marine snail Conus Bullatus. α-Conotoxin BuIA is a potent blocker of neuronal nicotinic acetylcholine receptors with interesting selectivity properties among isoforms. In particular, it discriminates best rat α6-subunit containing neuronal AChR over α4-containing receptors with respective IC50 values of 0.25 nM for α6/α3β2 chimeras and 10 µM for α4β2. However, the level of discrimination is mainly β-isoform dependent because the kinetics of unblock are dependent on the β-subunit type. Neuronal AChRs containing β4 rather than β2 have a very slow off rate for α-Conotoxin BuIA. This is true also for human AChRs. As a result, the IC50 values for α3β2 and α3β4 are, respectively, 5.7 nM and 27 nM and their Koff, respectively, 0.65 min-1 and 0.011 min-1. α-Conotoxin BuIA  can thus be advantageously used to discriminate between a-isoforms and also between β2 and β4 isoforms.

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