The T-1 conotoxin μ-SrVA from the worm hunting marine snail Conus spurius preferentially blocks the human Na1.5 channel.

Conotoxin sr5a had previously been identified in the vermivorous cone snail Conus spurius. This conotoxin is a highly hydrophobic peptide, with the sequence IINWCCLIFYQCC, which has a cysteine pattern "CC-CC" belonging to the T-1 superfamily. It is well known that this superfamily binds to molecular targets such as calcium channels, G protein-coupled receptors (GPCR), and neuronal nicotinic acetylcholine receptors (nAChR) and exerts an effect mainly in the central nervous system. However, its effects on other molecular targets are not yet defined, suggesting the potential of newly relevant molecular interactions. To find and demonstrate a potential molecular target for conotoxin sr5a electrophysiological assays were performed on three subtypes of voltage-activated sodium channels (Na1.5, Na1.6, and Na1.7) expressed in HEK-293 cells with three different concentrations of sr5a(200, 400, and 600 nM). 200 nM sr5a blocked currents mediated by Na1.5 by 33%, Na1.6 by 14%, and Na1.7 by 7%. The current-voltage (I-V) relationships revealed that conotoxin sr5a exhibits a preferential activity on the Na1.5 subtype; the activation of Na1.5 conductance was not modified by the blocking effect of sr5a, but sr5a affected the voltage-dependence of inactivation of channels. Since peptide sr5a showed a specific activity for a sodium channel subtype, we can assign a pharmacological family and rename it as conotoxin µ-SrVA.