ELECTROPHYSIOLOGICAL CHARACTERIZATION OF A NOVEL CONOTOXIN THAT BLOCKS MOLLUSCAN SODIUM-CHANNELS

A novel peptide toxin, PnIVB, isolated from the venom of Conus pennace us blocks voltage-gated sodium current in Aplysia neurons. Complete bl ockade is obtained at a PnIVB concentration of 80+/-2.2 nM and 50% blo ckade at 16+/-0.86 nM. The potency of PnIVB in blocking Aplysia sodium current is four orders of magnitude larger than that of tetrodotoxin. The toxin has no paralytic activity when injected into fish. The rapi d blockade of sodium current by PnIVB is not associated with a change in the activation or inactivation kinetics of the current, or with the reversal potential. Sodium current blockade is reversible after a 30 min wash with 50 times the bath volume. The novel conotoxin PnIVB can be used as a powerful tool for mollusc neurobiological research and as a molecular probe to explore the structure-function relations of volt age-gated sodium channel subtypes.