Molluscivorous Conus Toxins as Probes for Voltage and Ligand Gated Ion Channels in Molluscs

Venomous Conus snails are highly specific in their feeding ecology, and include a group of some 50 species that feed only on other molluscs. The present work was based on the hypothesis that molluscivorous Conus toxins have undergone targeting to unique sites in prey excitable systems, and may therefore serve as selective probes for molluscan ion channels. Over the past four years we have examined molluscivorous Conus venoms using in vivo bioassays (Patella, Mytilus), and pharmacological experiments in Helix CNS. Parallel assays have been performed by collaborating groups using clectrophysiological techniques on isolated Aplysia or Lymnaea neurons. A series of mollusc selective toxins have been characterized both chemically and pharmacologically. All the toxins are small (16-32 amino acid residues) cysteine-rich peptides. They differ from most previously characterized conotoxins in their charge, and in their relatively high content of hydrophobic residues. From the pharmacological point of view three categories of toxins have been characterized so far: (1) neuronal acctylcholine receptor blockers; (2) sodium channel blockcrs; and (3) toxins that slow inactivation of sodium channels. In addition, recent observations in Lymnaea systems suggest the existence of a number of calcium channel blockers in molluscivorous Conus venoms. These toxins provide useful tools for neurobiologists working with molluscan models, and are extremely selective probes for ion channel structure and function.

Affiliations: 1: Dept. of Cell & Animal Biology, Silberman Life Sciences Institute, Hebrew University, 91904 Jerusalem, Israel, Molecular Neurobiology, Faculty of Biology, Free University of Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands; 2: Dept. of Cell & Animal Biology, Silberman Life Sciences Institute, Hebrew University, 91904 Jerusalem, Israel