RT Journal Article
SR Electronic
T1 μ-Conotoxin PIIIA, a New Peptide for Discriminating among Tetrodotoxin-Sensitive Na Channel Subtypes
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4473
OP 4481
DO 10.1523/JNEUROSCI.18-12-04473.1998
VO 18
IS 12
A1 Ki-Joon Shon
A1 Baldomero M. Olivera
A1 Maren Watkins
A1 Richard B. Jacobsen
A1 William R. Gray
A1 Christina Z. Floresca
A1 Lourdes J. Cruz
A1 David R. Hillyard
A1 Anette Brink
A1 Heinrich Terlau
A1 Doju Yoshikami
YR 1998
UL http://www.jneurosci.org/content/18/12/4473.abstract
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.