PT  - JOURNAL ARTICLE
AU  - Ki-Joon Shon
AU  - Baldomero M. Olivera
AU  - Maren Watkins
AU  - Richard B. Jacobsen
AU  - William R. Gray
AU  - Christina Z. Floresca
AU  - Lourdes J. Cruz
AU  - David R. Hillyard
AU  - Anette Brink
AU  - Heinrich Terlau
AU  - Doju Yoshikami
TI  - μ-Conotoxin PIIIA, a New Peptide for Discriminating among Tetrodotoxin-Sensitive Na Channel Subtypes
AID  - 10.1523/JNEUROSCI.18-12-04473.1998
DP  - 1998 Jun 15
TA  - The Journal of Neuroscience
PG  - 4473--4481
VI  - 18
IP  - 12
4099  - http://www.jneurosci.org/content/18/12/4473.short
4100  - http://www.jneurosci.org/content/18/12/4473.full
SO  - J. Neurosci.1998 Jun 15; 18
AB  - 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.