KALICLUDINES AND KALISEPTINE - 2 DIFFERENT CLASSES OF SEA-ANEMONE TOXINS FOR VOLTAGE-SENSITIVE K+ CHANNELS

New peptides have been isolated from the sea anemone Anemonia sulcata which inhibit competitively the binding of I-125-dendrotoxin I (a clas sical ligand for K+ channel) to rat brain membranes and behave as bloc kers of voltage-sensitive K+ channels. Sea anemone kali-cludines are 5 8-59-amino acid peptides cross-linked with three disulfide bridges. Th ey are structurally homologous both to dendrotoxins which are snake ve nom toxins and to the basic pancreatic trypsin inhibitor (Kunitz inhib itor) and have the unique property of expressing both the function of dendrotoxins in blocking voltage-sensitive K+ channels and the functio n of the Kunitz inhibitor in inhibiting trypsin. Kaliseptine is anothe r structural class of peptide comprising 36 amino acids with no sequen ce homology with kalicludines or with dendrotoxins. In spite of this s tructural difference, it binds to the same receptor site as dendrotoxi n and kalicludines and is as efficient as a K+ channel inhibitor as th e most potent kalicludine.