%0 Journal Article %A Ki-Joon Shon %A Baldomero M. Olivera %A Maren Watkins %A Richard B. Jacobsen %A William R. Gray %A Christina Z. Floresca %A Lourdes J. Cruz %A David R. Hillyard %A Anette Brink %A Heinrich Terlau %A Doju Yoshikami %T μ-Conotoxin PIIIA, a New Peptide for Discriminating among Tetrodotoxin-Sensitive Na Channel Subtypes %D 1998 %R 10.1523/JNEUROSCI.18-12-04473.1998 %J The Journal of Neuroscience %P 4473-4481 %V 18 %N 12 %X We report the characterization of a new sodium channel blocker, μ-conotoxin PIIIA (μ-PIIIA). The peptide has been synthesized chemically and its disulfide bridging pattern determined. The structure of the new peptide is: where Z = pyroglutamate andO = 4-trans-hydroxyproline.We demonstrate that Arginine-14 (Arg14) is a key residue; substitution by alanine significantly decreases affinity and results in a toxin unable to block channel conductance completely. Thus, like all toxins that block at Site I, μ-PIIIA has a critical guanidinium group.This peptide is of exceptional interest because, unlike the previously characterized μ-conotoxin GIIIA (μ-GIIIA), it irreversibly blocks amphibian muscle Na channels, providing a useful tool for synaptic electrophysiology. Furthermore, the discovery of μ-PIIIA permits the resolution of tetrodotoxin-sensitive sodium channels into three categories: (1) sensitive to μ-PIIIA and μ-conotoxin GIIIA, (2) sensitive to μ-PIIIA but not to μ-GIIIA, and (3) resistant to μ-PIIIA and μ-GIIIA (examples in each category are skeletal muscle, rat brain Type II, and many mammalian CNS subtypes, respectively). Thus, μ-conotoxin PIIIA provides a key for further discriminating pharmacologically among different sodium channel subtypes. %U https://www.jneurosci.org/content/jneuro/18/12/4473.full.pdf