PubMed 25406007

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1 , Nav1.1 , Nav1.2 , Nav1.3 , Nav1.4 , Nav1.7

Title: Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity.

Authors: Brad R Green, Grzegorz Bulaj, Raymond S Norton

Journal, date & volume: Future Med Chem, 2014 Oct , 6, 1677-98

PubMed link:

μ-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified µ-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of µ-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty µ-conotoxin sequences have been identified to date and structure-activity relationship studies of several of these identified key residues responsible for interactions with VGSC subtypes. Efforts to engineer-in subtype specificity are driven by in vivo analgesic and neuromuscular blocking activities. This review summarizes structural and pharmacological studies of µ-conotoxins, which show promise for development of selective blockers of NaV1.2, and perhaps also NaV1.1,1.3 or 1.7.