MERCURY (HG2+) AND ZINC (ZN2+) - 2 DIVALENT-CATIONS WITH DIFFERENT ACTIONS ON VOLTAGE-ACTIVATED CALCIUM-CHANNEL CURRENTS

1. We examined the actions of mercury (Hg2+) and zinc (Zn2+) on voltage-activated calcium channel currents of cultured rat dorsal root ganglion (DRG) neurons, using the whole-cell patch clamp technique. 2. Micromolar concentrations of both cations reduced voltage-activated calcium channel currents. Calcium channel currents elicited by voltage jumps from a holding potential of -80 to 0 mV (mainly L- and N-currents) were reduced by Hg2+ and Zn2+. The threshold concentration for Hg2+ effects was 0.1 mu M and that for Zn2+ was 10 mu M. Voltage-activated calcium channel currents were abolished (>80%) with 5 mu M Hg2+ or 200 mu M Zn2+. The peak calcium current was reduced to 50% (IC50) by 1.1 mu M Hg2+ or 69 mu M Zn2+. While Zn2+ was much more effective in reducing the T-type calcium channel current-activated by jumping from -80 to -35 mV-Hg2+ showed some increased effectiveness in reducing this current. 3. The effects of both cations occurred rapidly and a steady state was reached within 1-3 min. While the action of Zn2+ was not dependent on an open channel state, Hg2+ effects depended partially on channel activation. 4. While both metal cations reduced the calcium channel currents over the whole voltage range, some charge screening effects were detected with Hg2+ and with higher concentrations (>100 mu M) of Zn2+. 5. As Zn2+ in the concentration range used had no influence on resting membrane currents, Hg2+ caused a clear inward current at concentrations greater than or equal to 2 mu M. 6. In the present study we discuss whether the actions of both metals on voltage-activated calcium channel currents are mediated through the same binding site and how they may be related to their neurotoxic effects.