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Kappa Conotoxins

Terlau, H., Shon, K-J., Grilley, M., Stocker, M., Stuhmer, W. and Olivera, B.M. (1996) Strategy for rapid immobilization of prey by a fish-hunting marine snail. Nature 381: 148-151.

[Conus purpurascens, alphaA-conotoxin, mu-conotoxin PIIIA, k-conotoxin PVIIA and delta-conotoxin PVIA. ( C.purpurascens venom contains at least three paralytic toxins, which act by blocking neuromuscular transmission; two of these, alphaA-conotoxin PIVA, which targets the nicotinic acetylcholine receptor, and mu-conotoxin PIIIA, which blocks skeletal muscle sodium channels, are not responsible for the rigid immobilization characteristic of excitotoxic shock and sudden tetanus of prey (STOP) syndrome which is brought about by a newly characterized peptide, 'fin-popping peptide' (k-conotoxin PVIIA), which inbibits the Shaker potassium channel, and the 29 amino-acid 'lock-jaw peptide' (delta-conotoxin PVIA) which delays sodium channel inactivation. Amino-acid sequence determination of k-conotoxin PVIIA shows it to be a 27 amino-acid peptide with the sequence : CRIONQKCFQHLDDCCSRKCNRFNKCV, where 'O' represents 4-trans-hydroxyproline. This 'fin-popping' peptide is the first member of a putative k-conotoxin family of K+ channel-targetted peptides. The authors have named it k-conotoxin PVIIA (k-PVIIA). At 1uM it had no effect on type II Na+ channels or the K+ channels Kv1.1 or Kv1.4 from rat brain (unpublished data).

Summary: When C.purpurascens stings fish, STOP is elicited by two excitotoxins, one increasing Na+ influx, the other decreasing K+ efflux, leading to powerful depolarization of cells. The AChR receptor inhibitor (alphaA-conotoxin PIVA) and the voltage gated Na+ channel inhibitor (mu-conotoxin PIIIA) cause neuromuscular block and flaccid paralysis, which occur SLOWLY owing to the dispersal time to synapses, however, k-PVIIA and delta-PVIA cause RAPID excitotoxic shock to immobilize prey quickly. The immobilization of prey by C.purpurascens resembles that by sea anemones (that initially contact their prey with a single tentacle) which have convergently evolved Na+ and K+ channel-targeted excitotoxins analagous to those used by C.purpurascens].

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