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Science 20 December 1985:
Vol. 230. no. 4732, pp. 1338 - 1343
DOI: 10.1126/science.4071055
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Articles

Science, Vol 230, Issue 4732, 1338-1343
Copyright © 1985 by American Association for the Advancement of Science

articles

Peptide neurotoxins from fish-hunting cone snails

BM Olivera, WR Gray, R Zeikus, JM McIntosh, J Varga, J Rivier, V de Santos, and LJ Cruz

To paralyze their more agile prey, the venomous fish-hunting cone snails (Conus) have developed a potent biochemical strategy. They produce several classes of toxic peptides (conotoxins) that attack a series of successive physiological targets in the neuromuscular system of the fish. The peptides include presynaptic omega-conotoxins that prevent the voltage-activated entry of calcium into the nerve terminal and release of acetylcholine, postsynaptic alpha-conotoxins that inhibit the acetylcholine receptor, and muscle sodium channel inhibitors, the mu-conotoxins, which directly abolish muscle action potentials. These distinct peptide toxins share several common features: they are relatively small (13 to 29 amino acids), are highly cross-linked by disulfide bonds, and strongly basic. The fact that they inhibit sequential steps in neuromuscular transmission suggests that their action is synergistic rather than additive. Five new omega-conotoxins that block presynaptic calcium channels are described. They vary in their activity against different vertebrate classes, and also in their actions against different synapses from the same animal. There are susceptible forms of the target molecule in peripheral synapses of fish and amphibians, but those of mice are resistant. However, the mammalian central nervous system is clearly affected, and these toxins are thus of potential significance for investigating the presynaptic calcium channels.


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The T-superfamily of Conotoxins.
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The Block of Shaker K+ Channels by {kappa}-Conotoxin Pviia Is State Dependent.
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Spontaneous activity regulates calcium-dependent K+ current expression in developing ascidian muscle.
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J. Physiol. 511, 683-693
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L-Type Calcium Channels Mediate a Slow Excitatory Synaptic Transmission in Rat Midbrain Dopaminergic Neurons.
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µ-Conotoxin PIIIA, a New Peptide for Discriminating among Tetrodotoxin-Sensitive Na Channel Subtypes.
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Biophysical and Pharmacological Characterization of Voltage-Dependent Ca2+ Channels in Neurons Isolated From Rat Nucleus Accumbens.
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E.E. Just Lecture, 1996. Conus Venom Peptides, Receptor and Ion Channel Targets, and Drug Design: 50 Million Years of Neuropharmacology.
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Diversity of Conus neuropeptides.
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Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons.
L. Hirning, A. Fox, E. McCleskey, B. Olivera, S. Thayer, R. Miller, and R. Tsien (1988)
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Multiple calcium channels and neuronal function.
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Residue Gly1326 of the N-type Calcium Channel alpha 1B Subunit Controls Reversibility of omega -Conotoxin GVIA and MVIIA Block.
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Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels.
M. Ino, T. Yoshinaga, M. Wakamori, N. Miyamoto, E. Takahashi, J. Sonoda, T. Kagaya, T. Oki, T. Nagasu, Y. Nishizawa, et al. (2001)
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