MERCURY (HG2-GATED CALCIUM-CHANNEL CURRENTS IN RAT DRG AND APLYSIA NEURONS() DECREASES VOLTAGE)

Inorganic mercury (Hg2+) reduced voltage-gated calcium channel current s irreversibly in two different preparations. In cultured rat dorsal r oot ganglion (DRG) neurons, studied with the whole cell patch clamp te chnique, a rapid concentration-dependent decrease in the L/N-type curr ents to a steady state was observed with an IC50 Of 1.1 mu M and a Hil l coefficient of 1.3. T-currents were blocked with Hg2+ in the same co ncentration range (0.5-2 mu M). With increasing Hg2+ concentrations a slow membrane current was additionally activated, most obviously at co ncentrations over 2 mu M Hg2+. This current was irreversible and might be due to the opening of other (non-specific) ion channels by Hg2+ Th e current-voltage (I-V) relation of DRG neurons shifted to more positi ve values, suggesting a binding of Hg2+ to the channel protein and/or modifying its gating properties. In neurons of the abdominal ganglion of Aplysia californica, studied with the two electrode voltage clamp t echnique, a continous decrease of calcium channel currents was seen ev en with the lowest used concentration of Hg2+ (5 mu M). A steady state was not reached and the effect was irreversible without any change on resting membrane currents, even with high concentrations (up to 50 mu M). No shift of the I-V relation of the calcium channel currents was observed. Effects on voltage-activated calcium channel currents with H g2+ concentrations such low have not been reported before. We conclude that neurotoxic effects of inorganic mercury could be partially due t o the irreversible blockade of voltage-activated calcium channels.