We describe a new peptide conotoxin affecting sodium current inactivation, that competes on binding with -conotoxin TxVIA (TxVIA). The amino acid sequence of the new toxin, designated conotoxin NgVIA (NgVIA), is SKCFSOGTFCGIKOGLCCSVRCFSLFCISFE (where O is trans-4-hydroxyproline). The primary structure of NgVIA has an identical cysteine framework and similar hydrophobicity as TxVIA but differs in its net charge. NgVIA competes with TxVIA on binding to rat brain synaptosomes and molluscan central nervous system and strongly inhibits sodium current inactivation in snail neurons, as does TxVIA. In contrast to TxVIA, NgVIA is a potent paralytic toxin in vertebrate systems, its binding appears to be voltage-dependent, and it synergically increases veratridine-induced sodium influx to rat brain synaptosomes. TxVIA acts as a partial antagonist to NgVIA in rat brain in vivo. NgVIA appears to act via a receptor site distinct from that of TxVIA but similar to that of Conus striatus toxin. This new toxin provides a lead for structure-function relationship studies in the -conotoxins and will enable analysis of the functional significance of this complex of receptor sites in gating mechanisms of sodium channels.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M.-M. Zhang, B. R. Green, P. Catlin, B. Fiedler, L. Azam, A. Chadwick, H. Terlau, J. R. McArthur, R. J. French, J. Gulyas, et al. Structure/Function Characterization of {micro}-Conotoxin KIIIA, an Analgesic, Nearly Irreversible Blocker of Mammalian Neuronal Sodium Channels J. Biol. Chem., October 19, 2007; 282(42): 30699 - 30706. [Abstract] [Full Text] [PDF]

				J. Ekberg, A. Jayamanne, C. W. Vaughan, S. Aslan, L. Thomas, J. Mould, R. Drinkwater, M. D. Baker, B. Abrahamsen, J. N. Wood, et al. {micro}O-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits PNAS, November 7, 2006; 103(45): 17030 - 17035. [Abstract] [Full Text] [PDF]

				L. Cohen, N. Lipstein, and D. Gordon Allosteric interactions between scorpion toxin receptor sites on voltage-gated Na channels imply a novel role for weakly active components in arthropod venom FASEB J, September 1, 2006; 20(11): 1933 - 1935. [Abstract] [Full Text] [PDF]

				P. J. West, G. Bulaj, and D. Yoshikami Effects of {delta}-Conotoxins PVIA and SVIE on Sodium Channels in the Amphibian Sympathetic Nervous System J Neurophysiol, December 1, 2005; 94(6): 3916 - 3924. [Abstract] [Full Text] [PDF]

				W. Ulbricht Sodium Channel Inactivation: Molecular Determinants and Modulation Physiol Rev, October 1, 2005; 85(4): 1271 - 1301. [Abstract] [Full Text] [PDF]

				L. Volpon, H. Lamthanh, J. Barbier, N. Gilles, J. Molgo, A. Menez, and J.-M. Lancelin NMR Solution Structures of {delta}-Conotoxin EVIA from Conus ermineus That Selectively Acts on Vertebrate Neuronal Na+ Channels J. Biol. Chem., May 14, 2004; 279(20): 21356 - 21366. [Abstract] [Full Text] [PDF]

				J. Barbier, H. Lamthanh, F. Le Gall, P. Favreau, E. Benoit, H. Chen, N. Gilles, N. Ilan, S. H. Heinemann, D. Gordon, et al. A {delta}-Conotoxin from Conus ermineus Venom Inhibits Inactivation in Vertebrate Neuronal Na+ Channels but Not in Skeletal and Cardiac Muscles J. Biol. Chem., February 6, 2004; 279(6): 4680 - 4685. [Abstract] [Full Text] [PDF]

				T. Kohno, T. Sasaki, K. Kobayashi, M. Fainzilber, and K. Sato Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist delta -Conotoxin TxVIA J. Biol. Chem., September 20, 2002; 277(39): 36387 - 36391. [Abstract] [Full Text] [PDF]

				S. Cestèle, R. B. Khalifa, M. Pelhate, H. Rochat, and D. Gordon [IMAGE]-Scorpion Toxins Binding on Rat Brain and Insect Sodium Channels Reveal Divergent Allosteric Modulations by Brevetoxin and Veratridine J. Biol. Chem., June 23, 1995; 270(25): 15153 - 15161. [Abstract] [Full Text] [PDF]