Discovery and characterization of the short κA-conotoxins: A novel subfamily of excitatory conotoxins

Russell W. Teichert*, Richard Jacobsen, Heinrich Terlau, Doju Yoshikami, Baldomero M. Olivera

*Corresponding author for this work
18 Citations (Scopus)


We have characterized the defining members of a novel subfamily of excitatory conotoxins, the short κA-conotoxins (κAS-conotoxins). κA-conotoxins PIVE and PIVF (κA-PIVE and κA-PIVF) were purified from Conus purpurascens venom. Both peptides elicited excitatory activity upon injection into fish. κA-PIVE was synthesized for further characterization. The excitatory effects of κA-PIVE in vivo were dose dependent, causing hyperactivity at low doses and rapid immobilization at high doses, symptomatic of a type of excitotoxic shock. Consistent with these observations, κA-PIVE caused repetitive action potentials in frog motor axons in vitro. Similar results have been reported for other structurally distinct conotoxin families; such peptides appear to be required by most fish-hunting cone snails for the rapid immobilization of prey. Unexpected structure-function relationships were revealed between these peptides and two families of homologous conotoxins: the αA-conotoxins (muscle nAChR antagonists) and κA-conotoxins (excitotoxins), which all share a common arrangement of cysteine residues (CC-C-C-C-C). Biochemically, the κAS-conotoxins more closely resemble the αAS-conotoxins than the other κA-conotoxin subfamily, the long κA-conotoxins (κAL-conotoxins); however, κAS- and αAS-conotoxins produce different physiological effects. In contrast, the κAS-and κAL-conotoxins that diverge in several biochemical characteristics are clearly more similar in their physiological effects.

Original languageEnglish
Issue number3
Pages (from-to)318-328
Number of pages11
Publication statusPublished - 01.03.2007

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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