Effects of mercurials on ligand- and voltage-gated ion channels: a review.
Both organic and inorganic mercurials are neurotoxic, an action attributable to their prominent reactivity with numerous biological ligands. While many sites within the central nervous system can be potentially affected by mercurials, ligand-and voltage-gated ion channels represent a plausible early target. There are several reasons for this. First, ion channels are located on the plasma membrane in large numbers, thus increasing the likelihood of mercurial-channel interaction. Second, ion channels may allow the passage of mercurials of similar size and charge as those ions which normally pass through the channel, a process which can hinder physiologic ion transport and also lead to disruption of intracellular events. Third, all mercurials have a high affinity for sulfhydryl groups on cysteines which may comprise critical regions of an ion channel. Consistent with an ability of neurotoxic metals to disrupt ion channel function, other heavy metals such as Cd2+, Pb2+, Co2+ and Zn2+ inhibit agonist binding to ligand-gated ion channels and inhibit ion flux through both ligand- and voltage-gated ion channels. Ion channels play a crucial role in cellular homeostasis. Changes in the intracellular concentrations of ions, necessary to initiate and sustain processes such as neurotransmitter release, growth cone elongation and gene expression, arise at least in part via flux through voltage- and ligand-gated ion channels. Since such a large battery of events are mediated by ion channels, it follows that their disruption by mercurials could lead to potentially deleterious consequences for the cell. This review will focus on the possible role that alteration in ion channel function may play in the pathological events seen following exposure either in vivo or in vitro to mercurials, and in particular methylmercury (MeHg).
Sirois
J E
JE
Department of Pharmacology, Michigan State University, East Lansing 48824-1317, USA.
Atchison
W D
WD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017669:Mercury Compounds / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D007473:Ion Channels; D017669:Mercury Compounds; D008767:Methylmercury Compounds; D002118:Calcium