A disulfide tether stabilizes the block of sodium channels by the conotoxin μO§-GVIIJ

A biochemically unique cone snail venom peptide has been characterized that may be used to probe unexplored but important features of the diverse voltage-gated Na channel isoforms that underlie electrical signaling in the nervous system. This peptide has a unique posttranslational modification (S-cysteinylated cysteine) and blocks sodium channels by forming a disulfide bond with the channel at a distinctive binding site. Because block by the peptide is prevented when specific β-subunits are coexpressed, this neurotoxin has potential for assessing which β-subunits are present in native Na channels. Peptide activity depends on the oxidation state of extracellular Cys residues on the channel. Thus, this peptide can also be used to monitor the oxidation state of the targeted Na channels.