Synthetic μO-conotoxin MrVIB blocks TTX-resistant sodium channel Na V1.8 and has a long-lasting analgesic activity

Grzegorz Bulaj*, Min Min Zhang, Brad R. Green, Brian Fiedler, Richard T. Layer, Sue Wei, Jacob S. Nielsen, Scott J. Low, Brian D. Klein, John D. Wagstaff, Linda Chicoine, T. Patrick Harty, Heinrich Terlau, Doju Yoshikami, Baldomero M. Olivera

*Corresponding author for this work
77 Citations (Scopus)

Abstract

μO-Conotoxin MrVIB is a blocker of voltage-gated sodium channels, including TTX-sensitive and -resistant subtypes. A comprehensive characterization of this peptide has been hampered by the lack of sufficient synthetic material. Here, we describe the successful chemical synthesis and oxidative folding of MrVIB that has made an investigation of the pharmacological properties and therapeutic potential of the peptide feasible. We show for the first time that synthetic MrVIB blocks rat NaV1.8 sodium channels and has potent and long-lasting local anesthetic effects when tested in two pain assays in rats. Furthermore, MrVIB can block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations from rat. Our work provides the first example of analgesia produced by a conotoxin that blocks sodium channels. The emerging diversity of antinociceptive mechanisms targeted by different classes of conotoxins is discussed.

Original languageEnglish
JournalBiochemistry
Volume45
Issue number23
Pages (from-to)7404-7414
Number of pages11
ISSN0006-2960
DOIs
Publication statusPublished - 13.06.2006

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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