Methylmercury effects on ion channels and electrical activity in neurons: Future directions

Methylmercury (CH3Hg+) is a potent neurotoxicant in humans and laboratory a nimals, and both epidemiological and laboratory data suggest that the devel oping nervous system is more susceptible to CH3Hg+ neurotoxicity than is th e adult nervous system. While it is recognized that the developing nervous system is more susceptible to CH3Hg+ neurotoxicity compared to the adult ne rvous system, it is presently not clear what level of exposure, if any, is without effect on the developing human nervous system. A better understandi ng of mechanisms of action of CH3Hg+ for developmental neurotoxicity would be useful in defining risks associated with CH3Hg+ exposure. While alterati ons in a variety of processes may contribute to the neurotoxicity of CH3Hg, changes in ion channel function and electrical activity in neuronal cells is a consistent observation following acute exposure in a variety of prepa rations. Additional research, however, is needed to clarify the relationshi p between alterations in neuronal electrophysiological function and develop mental neurotoxicity of CH3Hg+. This article suggests several issues to be considered in order to address the relationship between in vitro acute effe cts of CH3Hg+ on ion channels and electrophysiological function in neurons and developmental neurotoxicity. Future studies need: 1) to examine effects on ion channel function and neuronal electrophysiology following subacute and chronic in vitvo exposure to CH3Hg+; 2) to utilize model systems which consider developmental changes in neuronal function; 3) to consider direct vs. indirect effects of CH3Hg+; 4) to compare in vitro to ex vivo and in vi vo effect; 5) to utilize in vitro dose levels which reflect in vivo exposur e, and 6) to consider interactions between CH3Hg+ and other potential neuro toxicants found in environmental mixtures. Ultimately, it may be possible t o develop biologically-based dose-response models of CH3Hg+ neurotoxicity w hich will be useful in assessing the risks of developmental neurotoxicity o f this metal.