γ-Conotoxin-PnVIIA, A γ-Carboxyglutamate-Containing Peptide Agonist of Neuronal Pacemaker Cation Currents

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Abstract
A novel γ-carboxyglutamate-containing peptide, designated γ-conotoxin-PnVIIA, is described from the venom of the molluscivorous snail Conus pennaceus. γPnVIIA triggers depolarization and firing of action potential bursts in the caudodorsal neurons of Lymnaea. This effect is due to activation or enhancement of a slow inward cation current that may underly endogenous bursting activity of these neurons. The amino acid sequence of γPnVIIA was determined as DCTSWFGRCTVNSγCCSNSCDQTYCγLYAFOS (where γ is γ-carboxyglutamate, O is trans-4-hydroxyproline), thus γPnVIIA belongs to the six cysteine four loop structural family of conotoxins, and is most homologous to the previously described excitatory conotoxin-TxVIIA. Interestingly, TxVIIA did not induce action potentials in Lymnaea caudodorsal neurons. γPnVIIA is the prototype of a new class of γ-conotoxins that will provide tools for the study of voltage-gated pacemaker channels, which underly bursting processes in excitable systems.