Characterization of the neurotoxic constituents of Conus geographus (L) venom

Abstract

The crude venom of the marine gastropod Conus geographus (L) has been separated into three lethal constituents and their actions at the mammalian neuromuscular junction examined. Chromatography of the venom of Sephadex G-50 gave one toxic fraction, which was resolved by ion exchange chromatography on SP-Sephadex into three toxic components. These components were individually purified by diafiltration and Sephadex G-15 chromatography to give Toxins I,II and III. Toxins I and II in concentrations greater than 5 ug/ml reduced the amplitude of end-plate potentials and miniature end-plate potentials; Toxin I also blocked the depolarization of muscle fibres produced by carbachol; neither toxin affected the generation of action potentials in muscle fibres. Toxin III in concentrations greater than 5 ug/ml rapidly and reversibly blocked the generation of action potentials in muscle fibres; it had no effect on resting membrane potential nor on the amplitude of epps or mepps. It also slowly blocked the compound action potential recorded from isolated sciatic nerves but this was not reversible in the experiments. The rate at which this toxin blocked action potentials was increased by stimulation of the preparation. It is suggested that Toxin III acts by blocking the inward movement of sodium during activity. Toxin III appeared to be a nonadeca or eicosa peptide possibly having a cystine residue in the N-terminal position.