Chemical and electrophysiological characterization of new peptide neurotoxins from the venom of the molluscivorous snail conus textile neovicarius: A review

Three peptide toxins exhibiting strong paralytic activity to molluscs, but with no paralytic effects on arthropods or vertebrates, were purified from the venom of the molluscivorous snail Conus textile neovicarius from the Red Sea. The amino acid sequences of these mollusc specific toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCIVLVCT (identical to the so-called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGYCIVFVCT; TxIIA, WGGYSTYCγVDSγCCSDNCVRSYCT (γ=γ-carboxyglutamate). There is a similarity of the Cys framework of these toxins to that of the ω-conotoxins; however, their net negative charges, high content of hydrophobic residues, and uneven number of Cys residues in TxIIA are highly unusual for conotoxins. When assayed on isolated cultured Aplysia neurons, all three toxins induced spontaneous repetitive firing. The TxI toxins also induced a marked prolongation of the action potential duration. Voltage clamp experiments revealed that the TxI toxins alter the kinetics of the sodium current either by slowing down the rate of sodium current inactivation, or by recruiting silent sodium channels with slower activation and inactivation kinetics. The toxins shift the voltage-dependent steady-state Na⁺ current inactivation curve to more positive values by 6 mV. These changes are not associated with alteration in the rate of I(Na)+ activation, in the peak I,(Na)+, or the sodium current reversal potential. TxI represents a new class of conotoxins with an unusual phylogenic specificity and may therefore be useful as a probe for the study of voltage gated sodium channels. (This review summarizes previously published papers).