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 of a long-lasting hyperpolarization. The dual phase effect of the venom and the toxin persists even when synaptic input is eliminated either by axotomy, or by recording from freshly dissociated neurons or from neurons in primary cell culture. The ionic currents affected are an inward current, INSR, which is activated upon depolarization and an anomalously rectifying potassium current, IR, which is activated upon hyperpolarization. In the first phase of toxin action INSR is increased. In the second phase both the venom and the toxin block INSR and increase IR. The toxin effects may be due to complex alteration of one or more second messenger cascades rather than a direct action on ion channels.

Neurotoxic aminoglycoside antibiotics are potent inhibitors of [125I]-Omega-Conotoxin GVIA binding to guinea-pig cerebral cortex membranes.

[125I]-Omega-Conotoxin GVIA, a blocker of neuronal (N-type) calcium channels labelled 295 +/- 121 fmol per mg protein of high affinity sites (apparent half-saturation at 1.5 to 2.5 pmol/l) in guinea-pig cerebral cortex membranes. Divalent cations (Cd2+ greater than Ni2+ greater than Co2+ greater than Ca2+ greater than Sr2+ = Ba2+ greater than Mg2+) and La3+ were potent inhibitors of Omega-Conotoxin GVIA binding, whereas monovalent cations (Na+, K+, Li+) were ineffective up to 50 mmol/l. Aminoglycosides (neomycin greater than gentamycin = tobramycin greater than streptomycin greater than amikacin greater than kanamycin) and polymyxin B also inhibited [125I]-Omega-Conotoxin GVIA binding with IC50 values in the mumolar range. All other antibiotics tested were ineffective up to 1 mmol/l. With the exception of polymyxin B, which partially inhibited the binding of the 1,4-dihydropyridine (+)-[3H]PN 200-110 and of (-)-[3H]desmethoxyverapamil, the aminoglycosides and the other antibiotics had no effect on the L-type calcium channel labelling. It is suggested, that inhibition of neurotransmitter release by aminoglycosides is mediated via blockade of the N-type calcium channel to which [125I]-Omega-Conotoxin GVIA binds selectively in a quasi irreversible manner.

Respiratory failure and lethal hypotension due to blue-ringed octopus and tetrodotoxin envenomation observed and counteracted in animal models.

The effects of crude blue-ringed octopus venom gland extract and tetrodotoxin (TTX) on anaesthetised rats and rabbits were studied. Paralysis of the respiratory musculature causing anoxia and cyanosis was overcome with positive, artificial respiration. The second lethal mechanism of the toxins: rapid and severe hypotension, had to be counteracted peripherally, since neural transmission had been drastically reduced by the toxins. Noradrenaline, d-amphetamine, phenylephrine and methoxamine, agonists acting on vascular adrenergic a-receptors, were tested.

[Preliminary studies of Conus geographus venom structural properties: evaluation of the toxin's molecular weight]. / Etudes préliminaires des propriétés structurales du venin de Conus geographus: évaluation du poids moléculaire de la toxine.

Venom from the posterior half of the venom duct of Conus Geographus was toxic to mice but without effect on a crab, and produced a flaccid spasmodic paralysis in mice. The minimum lethal dose for mice ranged from 5 micrograms to 50 micrograms (net weight) of venom per mouse. Toxin was submitted to Sephadex G 25 chromatography and to ultrafiltration. The venom was inactivated by pronase. The data suggested that the toxin was a peptide of molecular weight of about 1 500-2 000.