EFFECTS OF HG2-BRAIN MICROSOMES( AND CH3HG+ ON CA2+ FLUXES IN RAT)

A permanent increase in cytosolic Ca2+ levels seems to be associated w ith various pathological situations which may result in cell death. Hg 2+ and CH3Hg+ are potent neurotoxic agents, but the precise molecular mechanism(s) underlying their effects are not sufficiently understood. In the present study we investigated the potential role of Ca2+-ATPas e located in the endoplasmic reticulum as a molecular target for mercu ry. Hg2+ and CH3Hg+ inhibited Ca2+-ATPase and Ca2+ uptake by brain mic rosomes with similar potencies. However, the inhibitory potency of Hg2 + was higher than that of CH3Hg+, probably reflecting differences in t he affinity for the sulfhydryl groups of these compounds. Passive or u nidirectional Ca2+ efflux (measured in the absences of Ca2+-ATPase lig ands) was increased significantly by CH3Hg+ and Hg2+. Again, the poten cy of Hg2+ was higher than that of CH3Hg+. Blockers of Ca2+ channels ( ruthenium red, procaine, heparin) did not affect the increase in passi ve Ca2+ efflux induced by mercury compounds, possibly indicating that Ca2+ release occurs through Ca2+-ATPase. Addition of physiological con centrations of glutathione (GSH) simultaneously with mercury abolished the inhibitory effects of both forms of Hg on Ca2+-transport. However , if the enzyme was first inhibited with Hg2+ or CH3Hg+ and subsequent ly treated with GSH, the reversal of inhibition was about 50%, suggest ing that part of the cysteinyl residues involved in the inhibitory act ions of mercury in Ca2+-transport bind to mercury with an extremely hi gh affinity.