Blockade of [3H]lysine-tetrodotoxin binding to sodium channel proteins by conotoxin GIII.

Conotoxin GIII from Conus geographus inhibited the binding of [3H]lysine-tetrodotoxin (4 nM) to electroplax membranes from Electrophorus electricus and to the rat brain P2 fraction with IC50 values of 13 nM and 7.9 microM, respectively. This inhibition observed with electroplax membranes was irreversible. These and physiological findings (Life Sci., 21 (1977) 1759-1770 suggest that conotoxin GIII inhibits Na channel activation by its interaction with the tetrodotoxin binding site of the Na channel. The differences in structures related to the activation of Na channels between the eel electroplax and the rat brain are indicated.