Methylmercury effects on ion channels and electrical activity in neurons: future directions.
Methylmercury (CH3Hg+) is a potent neurotoxicant in humans and laboratory animals, and both epidemiological and laboratory data suggest that the developing nervous system is more susceptible to CH3Hg+ neurotoxicity than is the adult nervous system. While it is recognized that the developing nervous system is more susceptible to CH3Hg+ neurotoxicity compared to the adult nervous system, it is presently not clear what level of exposure, if any, is without effect on the developing human nervous system. A better understanding of mechanisms of action of CH3Hg+ for developmental neurotoxicity would be useful in defining risks associated with CH3Hg+ exposure. While alterations 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 preparations. Additional research, however, is needed to clarify the relationship between alterations in neuronal electrophysiological function and developmental neurotoxicity of CH3Hg+. This article suggests several issues to be considered in order to address the relationship between in vitro acute effects 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 vitro 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 vivo effects; 5) to utilize in vitro dose levels which reflect in vivo exposure, and 6) to consider interactions between CH3Hg+ and other potential neurotoxicants found in environmental mixtures. Ultimately, it may be possible to develop biologically-based dose-response models of CH3Hg+ neurotoxicity which will be useful in assessing the risks of developmental neurotoxicity of this metal.
Shafer
T J
TJ
Neurotoxicology Division Division (MD-74B), National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. shafer.tim@epamail.epa.gov
D000818:Animals; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D008767:Methylmercury Compounds / Q000378:metabolism* / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity
D007473:Ion Channels; D008767:Methylmercury Compounds; D009498:Neurotoxins