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 puri fied from the venom of the molluscivorous snail Conus textile neovicar ius from the Red Sea. The amino acid sequences of these mollusc specif ic toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCIVLVCT (identical to the so- called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGY-CIVFVCT; TxIIA , WGGYSTYCgammaVDSgammaCCSDNCVRSYCT (gamma= gamma-carboxyglutamate). T here is a similarity of the Cys framework of these toxins to that of t he omega-conotoxins; however, their net negative charges, high content of hydrophobic residues, and uneven number of Cys residues in TsIIA a re highly unusual for conotoxins.When assayed on isolated cultured Apl ysia neurons, all three toxins induced spontaneous repetitive firing. The TxI toxins also induced a marked prolongation of the action potent ial duration. Voltage clamp experiments revealed that the TxI toxins a lter the kinetics of the sodium current either by slowing down the rat e of sodium current inactivation, or by recruiting silent sodium chann els 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 al teration in the rate of I(Na+) activation, in the peak I(Na+) or the s odium current reversal potential. TxI represents a new class of conoto xins with an unusual phylogenic specificity and may therefore be usefu l as a probe for the study of voltage gated sodium channels. (This rev iew summarizes previously published papers).