Abstract
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 language | English |
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Journal | Toxicon |
Volume | 49 |
Issue number | 3 |
Pages (from-to) | 318-328 |
Number of pages | 11 |
ISSN | 0041-0101 |
DOIs | |
Publication status | Published - 01.03.2007 |
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)