Hg2+ causes neurotoxicity at an intracellular site following entry through Na and Ca channels

At motor nerve terminals, Hg2+ causes (a) irreversible depolarization, (b) increase in transmitter release, and (c) subsequent irreversible block of transmitter release. All effects are antagonized when a Na channel blocker (tetrodotoxin, TTX) and a Ca channel blocker (Co2+) are present, but not when either blocker is used alone. The effects are not antagonized by TTX plus Co2+ when the mercurial is lipid-soluble (methylmercury). This indicates that the neurotoxic action of Hg2+ is at an intracellular site and that entry is gained through both Na and Ca channels. The results suggest that metals may inhibit transmitter release at either the Ca channel or at the release site, but that irreversible toxicity is due to an intracellular action, possibly involving SH groups.