Comparative effects of charged and uncharged mercurials on 45C2+ uptake in rat forebrain synaptosomes

The relative blocking efficacy of methylmercury (MeHg), dimethylmercury (2MeHg) and mercuric chloride (Hg2+) on Ca2+ influx into rat forebrain synaptosomes was assessed in order to provide information as to the mechanism(s) by which mercurials interact with membrane Ca channels. 45Ca2+ uptake into synaptosomes was measured after 1 (fast, inactivating phase) and 10 (total) sec of depolarization by 77.5 mM KCl and during 10 sec of depolarization into synaptosomes that were previously depolarized for 10 sec in the presence of 77.5 mM K+ but no external Ca (slow, noninactivating phase). In the range tested (10-500 μM), total uptake, as well as the fast and slow components of 45Ca2+ influx into synaptosomes, were blocked in a concentration-dependent manner by both MeHg and Hg2+ (>10 μM). Hg2+ was a much more effective blocker of the slow phase of Ca influx with an estimated IC50 value of 25 μM, whereas MeHg was more effective at blocking the fast phase of uptake (IC50-150 μM). In contrast, 2MeHg (10-500 μM) produced no appreciable reduction in any phase of uptake. These results suggest that mercurials of dissimilar charge and lipophilicity, differentially affect 45Ca2+ influx into the synaptosome and likely have different mechanisms of action on synaptosomal membranes