Conus Textile Research Articles

Alterations of voltage-activated sodium current by a novel conotoxin from the venom of Conus gloriamaris

1. The novel peptide toxin delta-conotoxin-GmVIA, recently purified by us from the mollusk-hunting snail Conus gloriamaris, induces convulsive-like contractions when injected into land snails but has no detectable effects in mammals. 2. At concentrations of 0.5-0.75 microM, the toxin induces action potential broadening and increased excitability of cultured Aplysia neurons. 3. Whole cell patch-clamp experiments on cultured Aplysia neurons revealed that the toxin does not alter potassium or calcium currents, but induces action potential broadening by slowing the inactivation kinetics of the sodium current. Under control conditions, the inactivation kinetics of the sodium current follows a single exponential with tau = 0.47 +/- 0.14 (SE) ms. After toxin application the sodium current inactivation is composed of two phases: an early phase with tau = 0.86 +/- 0.12 ms and a late phase of slowly inactivating sodium current with tau = 488 +/- 120 ms. In addition, the toxin shifts the voltage-dependent steady-state inactivation curve to more positive values and the steady-state activation curve to more negative values. These alterations are not associated with changes in the rise time or the peak value of the sodium current. 4. The novel delta-conotoxin-GmVIA, and the previously described "King Kong peptide," purified from another mollusk-hunting cone (Conus textile), share a similar cystein framework also found in the calcium channel blocking peptide omega-conotoxin but represent a new class of conotoxins with unusual specificity for molluscan sodium channels.

A toxin from the venom of the predator snail Conus textile modulates ionic currents in Aplysia bursting pacemaker neuron

Conus textile crude venom and a peptide component (‘King Kong’ toxin) purified from this venom, alter membrane excitability of Aplysia neurons. Venom, applied to the medium bathing an abdominal ganglion, changes dramatically the electrical activity of bursting pacemaker neuron. The effects on bursting neuron R15 was examined in current-clamp and voltage-clamp modes. A dual phase effect of both the venom and the purified toxin were observed. The first phase starts immediately after venom or toxin application and is observed as an increase in membrane excitability, resulting in an enhancement of bursting. The second phase begins about 15 min later and consists ofa long-lasting hyperpolarization. The dual phase effect of the venom and the toxin persists even when synaptic input is eleminated either by axotomy, or by recording from freshly dissociated neurons of from neurons in primary cell culture. The ionic currents affected are an inward current, I nsr , which is activated upon depolarization and an anomalously rectifying potassium current, I R , which is activated upon hyperpolarization. In the first phase of toxin action I NSR is increased. In the second phase both teh venom and the toxin block I NSR and increase I R . The toxin effects may be due complex alteration of one or more second messenger cascades rather than a direct action on ion channels.

Conus Peptides: Phylogenetic Range of Biological Activity.

The major function of the venoms of the predatory marine snails belonging to the genus Conus is to paralyze prey. Thus, the venom of each Conus species acts on receptors and ion channels of the prey; previous studies suggested much less activity on homologous receptor targets in more distant taxa. In this article, we address the question of whether some peptide components of Conus venoms ("conopeptides") have "cross-phylum" biological activity. We examined the venom of Conus textile, a mollusk-hunting Conus, using a mammalian biological activity assay. We purified a 23 amino acid "convulsant peptide" with potent activity in the mammalian CNS, even though it comes from the venom of a snail-hunting Conus species. A survey of Conus textile venom fractions indicates that, in addition to the convulsant peptide, many other components of this venom will exhibit "cross-phylum" biological activity. Conopeptides with broad-range phylogenetic specificity should be useful tools for studying the evolution of receptors and ion channels, and of nervous systems.

Constant and hypervariable regions in conotoxin propeptides.

Conotoxins are small cysteine rich peptides found in the venom of the predatory cone snails (Conus) which have prove to be useful high affinity ligands for various receptors and ion channels. The first cloning data for conotoxins, reported here, were obtained for the King-Kong peptide, a 27 amino acid conotoxin found in the venom of the cloth-of-gold cone, Conus textile. Analysis of cDNA clones of the King-Kong peptide revealed a family of related toxin transcripts. Three different propeptide cDNA sequences were obtained; only one of these encoded sequence for the King-Kong peptide. The other cDNA sequences encoded two different peptides (KK-1 and KK-2). When the predicted propeptide sequences are compared, well defined conserved and hypervariable regions can be identified. The hypervariable regions comprise four regions between Cys residues in the final peptide toxins; the remainder of the propeptide sequences, i.e. the excised N-terminal regions and the disulfide bonded Cys residues, are highly conserved. We suggest that the conserved regions may direct the formation of a specific disulfide configuration in the King-Kong family of conotoxins.

A molluscivorous Conus toxin: conserved frameworks in conotoxins.

We purified and characterized a 27 amino acid toxin from a snail-hunting Conus venom, Conus textile. This toxin causes convulsive-like activity in snails and causes subordinate lobsters to assume an exaggerated dominant posture. The sequence of this peptide is Trp-Cys-Lys-Gln-Ser-Gly-Glu-Met-Cys-Asn-Leu-Leu-Asp-Gln-Asn-Cys-Cys-Asp- Gly-Tyr-Cys-Ile-Val-Leu-Val-Cys-Thr. The sequence was confirmed by determining the nucleotide sequence of a cDNA clone coding for the peptide. The conservation of Cys residues compared to the omega-conotoxins from piscivorous Conus venom suggests that toxins from different cone venoms may use only a few "Cys-motifs" as conserved structural backbones for targeting to a variety of receptors in different animals.

The occurrence of arachidonic acid in the venom duct of the marine snail conus textile.

A crude extract of the venom of the marine snailConus textile Linne caused a powerful contraction in the guinea-pig isolated ileum. The extract of the venom has been fractionated, and the fractions monitored by the contractile effect. Arachidonic acid was shown to be present as an active substance.

Pharmacological study on the venom of the marine snail Conus textile

The pharmacological effects of Conus textile venom on the rabbit aorta, the guinea-pig left atria, vas deferens and ileum, and the mouse diaphragm were examined. The venom caused a marked, transient contraction of the ileum which was abolished by atropine and tetrodotoxin. The venom exhibited a positive inotropic effect on the left atria which was almost completely inhibited by verapamil. Activity on the ileum was retained after heating at 70°C for 1 hr, exposure to 1 N HCl or 1 N NaOH and incubation with proteases. Active material(s) in the venom passed through a UM2 filter, suggesting a molecular weight lower than 1000.

Escape responses of three herbivorous gastropods to the predatory gastropod Conus textile

Summary The herbivorous gastropods Strombus canarium, Lambis lambis, and Trochus pyramis evince escape responses, probably mediated by distance chemoreception, in the presence of the predatory gastropod Conus textile. In Strombus and Lambis, the response has two components: increase in the absolute rate of locomotion, and direction of locomotion away from the predator. When placed in the presence of C. textile, T. pyramis began moving, generally in the direction it faced. In control observations, a specimen of S. canarium moved at a mean rate of 2·7 mm/sec, by the leaping mode of locomotion characteristic of this and related genera. In the presence of C. textile, the rate increased to 6·8 mm/sec, due primarily to shortening of the lag or recovery period between leaps. In the presence of C. textile, a specimen of L. lambis moved at a rate of 11·9 mm/sec in the same manner as Strombus. In the presence of C. textile, a specimen of T. pyramis progressed at a rate of 1·9 mm/sec, by pedal locomotory waves. Comparison with absolute rates of locomotion by pedal locomotory waves in other marine gastropod molluscs leads to the conclusion that the leaping of Strombus and Lambis does not enable these gastropods to maintain a more rapid long-term rate of movement, but it confers a striking increase in agility, and a single leap provides an almost instantaneous increase in distance from a potential predator.

Pharmacological investigation of the venoms of the marine snails Conus textile and Conus geographus

Phrenic nerve-diaphragm preparations and isolated skeletal muscles were exposed to two Conus venoms. Rats and mice were injected intraperitoneally. Anaesthetized rats and guinea-pigs were injected intravenously, the sciatic nerve being exposed and stimulated to give a foot twitch. Paralysis of diaphragm and other isolated muscles was observed only after administration of venom from the posterior half (approximately) of the venom duct of C. geographus. The anterior half of the duct of C. geographus and the whole of the duct of C. textile failed to yield venom capable of paralyzing isolated muscles or of causing symptoms in rats and mice on intraperitoneal injection. Venom active on isolated skeletal muscle caused respiratory failure in anaesthetized animals, the foot twitch response to sciatic nerve stimulation being simultaneously abolished. Recovery in both aspects usually occurred after artificial respiration. Active venom paralyzed skeletal muscle directly without prior neuromuscular blockade. However, there was enhancement of the effect of liminal doses of tubocurarine on the neuromuscular junction, and tubocurarine enhanced the muscle paralysis produced by small doses of venom. Eserine was without effect on the muscle paralysis.

On the Anatomy of Conus tulipa, Linn., and Conus textile, Linn

ABSTRACT SINCE 1895, few workers on the anatomy of mollusca have devoted their attention to the genus Conus. In that year Dr. Bergh (3) published an extensive memoir on a large number of species in this genus, and his work may be considered as the most complete, and embracing the greatest number of. species examined, though his description of each species was not exhaustive. Troschel (20) devoted most of his attention to the radulae of the different genera and species of which his excellent work is composed, and although he gives a certain number of figures with descriptions of various anatomical points, these latter are for the most part of rather a crude and diagrammatic kind.