MOLLUSCIVOROUS CONUS TOXINS AS PROBES FOR VOLTAGE AND LIGAND-GATED ION CHANNELS IN MOLLUSKS

Venomous Conus snails are highly specific in their feeding ecology, an d include a group of some 50 species that feed only on other molluscs. The present work was based on the hypothesis that molluscivorous Conu s toxins have undergone targeting to unique sites in prey excitable sy stems, and may therefore serve as selective probes for molluscan ion c hannels. Over the past four years we have examined molluscivorous Conu s venoms using in vivo bioassays (Patella, Mytilus), and pharmacologic al experiments in Helix CNS. Parallel assays have been performed by co llaborating groups using electrophysiological techniques on isolated,A plysia or Lymnaea neurons. A series of mollusc selective toxins have b een characterized both chemically and pharmacologically. All the toxin s are small (16-32 amino acid residues) cysteine-rich peptides. They d iffer from most previously characterized conotoxins in their charge, a nd in their relatively high content of hydrophobic residues. From the pharmacological point of view three categories of toxins have been cha racterized so far: (1) neuronal acetylcholine receptor blockers; (2) s odium channel blockers; and (3) toxins that slow inactivation of sodiu m channels. In addition, recent observations in Lymnaea systems sugges t the existence of a number of calcium channel blockers in molluscivor ous Conus venoms. These toxins provide useful tools for neurobiologist s working with molluscan models, and are extremely selective probes fo r ion channel structure and function.