GAMMA-CONOTOXIN-PNVIIA, A GAMMA-CARBOXYGLUTAMATE-CONTAINING PEPTIDE AGONIST OF NEURONAL PACEMAKER CATION CURRENTS

A novel gamma-carboxyglutamate-containing peptide, designated gamma-co notoxin-PnVIIA, is described from the venom of the molluscivorous snai l Conus pennaceus, gamma PnVIIA triggers depolarization and firing of action potential bursts in the caudodorsal neurons of Lymnaea. This ef fect is due to activation or enhancement of a slow inward cation curre nt that may underly endogenous bursting activity of these neurons. The amino acid sequence of gamma PnVIIA was determined as DCTSWFGRCTVNS g amma CCSNSCDQTYC gamma LYAFOS (where gamma is gamma-carboxyglutamate, O is trans-4-hydroxyproline), thus gamma PnVIIA belongs to the six cys teine four loop structural family of conotoxins, and is most homologou s to the previously described excitatory conotoxin-TxVIIA. Interesting ly, TxVIIA did not induce action potentials in Lymnaea caudodorsal neu rons. gamma PnVIIA is the prototype of a new class of gamma-conotoxins that will provide tools for the study of voltage-gated pacemaker chan nels, which underly bursting processes in excitable systems.