Conotoxine

Conotoxins, also spelled conotoxine in some sources, are small, cysteine-rich peptide toxins produced by predatory marine cone snails (genus Conus). They are delivered via venomous harpoons to immobilize prey and defend against threats. Each toxin is a short peptide stabilized by multiple disulfide bonds, often exhibiting high potency and selectivity for neural ion channels and receptors.

The conotoxin repertoire is highly diverse, with functional types including alpha-, omega-, mu-, delta-, and kappa-conotoxins. They are encoded as larger precursor proteins in the snail genome and processed into mature peptides with distinct cysteine frameworks. Thousands of distinct conotoxins have been identified, and many more are predicted.

Mechanistically, conotoxins target ion channels and receptors. Alpha-conotoxins block nicotinic acetylcholine receptors; omega-conotoxins block N-type voltage-gated calcium channels, inhibiting neurotransmitter release; mu-conotoxins block voltage-gated sodium channels. Delta-conotoxins modulate sodium channel inactivation, and kappa-conotoxins affect potassium channels. This diversity yields precise neuromodulatory effects.

Medical relevance includes ziconotide, a synthetic omega-conotoxin MVIIA, approved for intrathecal treatment of chronic pain. It achieves analgesia by blocking CaV2.2 channels but requires careful dosing due to potential neuropsychiatric side effects, limiting systemic use. Research continues on conotoxins as analgesics and pharmacological tools.

Discovery and research: Cone snails deploy venom through a specialized apparatus; toxins are isolated from venom ducts or produced synthetically. Conotoxins serve as powerful pharmacological probes and templates for drug design, helping to elucidate neural signaling and offering leads for new therapies.