Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.
Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.
['Dongol|Yashad|Y|0000-0003-3114-1167', 'Cardoso|Fernanda Caldas|FC|0000-0002-0068-9974', 'Lewis|Richard J|RJ|0000-0003-3470-923X']
D000595:Amino Acid Sequence D000818:Animals D006801:Humans D010146:Pain D013111:Spider Venoms D061567:Voltage-Gated Sodium Channel Blockers D061566:Voltage-Gated Sodium Channels
knottins voltage-gated sodium channel NaV chronic pain spider venom ICK peptide