EFFECTS OF INORGANIC MERCURY ON [H-3] DOPAMINE RELEASE AND CALCIUM HOMEOSTASIS IN RAT STRIATAL SYNAPTOSOMES

Inorganic mercury (Hg2+) in vitro increases spontaneous transmitter release from nerve terminals. The mechanisms of action are not well understood but may involve alterations in intraterminal Ca2+ dynamics. In this study we describe actions of Hg2+ in vitro on isolated mammalian CNS striatal nerve terminals (synaptosomes). Cobalt (2 mm) completely blocked the effect of 2 μm Hg2+ on spontaneous [3H]dopamine release. Cadmium (100 μm) was equipotent to Co2+ in blocking depolarization-dependent [3H]dopamine release, but did not alter the 2 μm Hg2+-induced spontaneous [3H]dopamine release. Depolarization-dependent [3H]dopamine release was not altered by 5 μm Hg2+. It appears that the site of action of Hg2+ on spontaneous [3H]dopamine release is not the Ca2+ channel. The effects of Hg2+ on intraterminal ionized Ca2+ ([Ca2+]i) were evaluated using the Ca2+-specific fluorescent probe, fura-2. Hg2+ (1-8 μm) had no effect on [Ca2+]i in 1.2 mm Ca2+-containing buffers. In nominal Ca2+ media, 4 and 8 μm Hg2+ significantly decreased [Ca2+]i. Following exposure to 4 and 8 μm Hg2+ the quenching of extrasynaptosomal fura-2 by Mn2+ was increased, suggesting that Hg2+ facilitated the leakage of fura-2. This apparent leakage was probably due to a nonspecific increase in membrane permeability since 2 μm Hg2+ produced a Co2+-insensitive increase in [3H]deoxyglucose phosphate efflux. Hg2+ (2-8 μm) did not increase the leakage of either lactate dehydrogenase or soluble protein from synaptosomes. Hg2+ produced a concentration-dependent (1-8 μm) increase in 45Ca2+ efflux from superfused synaptosomes which was insensitive to blockade either by 2 mm Co2+ or by 100 μm Cd2+. These data suggest that the transmitter releasing action of Hg2+ involves interactions with sites that also interact with Co2+ but not with Cd2+. Furthermore, Hg2+ may have direct transmitter releasing actions (i.e., Ca2+-mimetic properties), as well as nonspecific actions on plasma membrane permeability which may not necessarily be linked to [3H]dopamine release. © 1990.