Actions of 4-epitetrodotoxin and anhydrotetrodotoxin on the squid axon.

The actions of the newly discovered 4-epitetrodotoxin and of anhydrotetrodotoxin have been studied on the internally perfused squid giant axon under voltage-clamped conditions. Both compounds are selective in blocking only the sodium channel. The concentration for reducing the sodium current to one-half is 13.2 nM for 4-epitetrodotoxin and 298 nM for anhydrotetrodotoxin. Compared with tetrodotoxin, the relative potencies are 0.39 for 4-epitetrodotoxin and 0.018 for anhydrotetrodotoxin. The results suggest that hydrogen bonding at C-4 and C-9 is an important contributing force in binding to the membrane receptor site.