revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 213
2. HEALTH EFFECTS
At the functional level, both mercuric chloride and methylmercury have been shown to induce a slow
inward current in patch-clamped dorsal root ganglion cells (Arakawa et al. 1991). The current does not
appear to be mediated by either the sodium or calcium channels, but it may be activated by increases in
intracellular calcium. Such slow inward currents suppress voltage- and neurotransmitter-activated currents.
Studies of the effects of inorganic mercury, methylmercury, and phenylmercuric acetate on synaptic
transmission in rat hippocampal slices (Yuan and Atchison 1994) revealed that the mechanisms that
underlie the effects of various mercurials on central synaptic transmission differ with respect to the sites of
action, the potency, and the reversibility of the effect. Inorganic mercury (Hg ++ ) appeared to act primarily
on the postsynaptic neuronal membrane, whereas the action of methylmercury and phenylmercuric acetate
was at both the pre- and postsynaptic sites but primarily on the postsynaptic membranes. Yuan and
Atchison (1994) suggested that these differences may result, in part, from the differences in lipophilicity
among the different mercurials studied. Differences in lipophilicity were also implicated by Roed and
Herlofson (1994) as playing a role in the different effects produced by methylmercuric chloride and
mercuric chloride. Roed and Herlofson (1994) suggested that the high lipid solubility of methylmercuric
chloride may divert that organomercurial to the myelin of the nerve, where it very efficiently inhibits
neuronal excitability. Further, they suggested that mercuric chloride probably causes inhibitory activity by
binding to sulfhydryl groups in transport proteins that convey the messenger function of intracellular Ca ++ .
This, in turn, leads to both inhibition of muscle contraction and enhancement of HgCl2-induced neuronal
inhibition. The authors further suggest that HgCl2 inhibits an internal Ca ++ signal necessary for choline reuptake
and acetylcholine resynthesis.
Gallagher and Lee (1980) evaluated the similarity of inorganic and organic mercury toxicity to nervous
tissue by injecting equimolar concentrations of both mercuric chloride and methylmercuric acetate directly
into the cerebrum of rats, thereby circumventing systemic metabolic conversion pathways. The lesions
induced by mercuric chloride were expected to have been much greater after the mercuric chloride
injection, since this process circumvents the necessity for biotransformation. However, the lesions were
only slightly larger than those seen after methylmercury injection, suggesting that there is a mechanism for
organic mercury neurotoxicity that does not involve conversion into inorganic mercury. This suggestion is
supported by the findings of Magos et al. (1985) who failed to establish a correlation between neuronal,
cytoplasmic, mercuric ions and neuronal degeneration, or clinical evidence of neurotoxicity. These results
do not, however, preclude the possibility that intracellular transport of mercuric mercury may be limited,
and the limitations on transport may determine the effects observed.