MAMMALIAN VOLTAGE-ACTIVATED CALCIUM-CHANNEL CURRENTS ARE BLOCKED BY PB2+, ZN2+, AND AL3+

The effects of the di- and trivalent trace metal cations, Pb2+ Zn2+, and Al3+, on voltage-activated calcium channel currents recorded from cultured rat dorsal root ganglion neurons were determined. All three cations blocked transient and sustained components of the voltage-gated calcium channel currents elicited by a voltage jump from -80 mV to 0 mV, but the trace metals differed in threshold, reversibility, and specificity, and in actions on the different components. Pb2+ was most effective in reducing the voltage-activated calcium channel currents. Threshold concentration for Pb2+ was <0.1 mu M. The threshold for Zn2+ action was <5 mu M and that for Al3+ was similar to 20 mu M. Total blockade (>80%) was obtained with concentrations >1 mu M pb(2+), and 150-200 mu M Zn2+ or Al3+. Half of the current was blocked with 0.6 mu M Pb2+, 69 mu M Zn2+, and 84 mu M Al3+. The Hill slope for Pb2+ and Zn2+ action was similar to 1, whereas for Al3+ it was close to 3. Al3+ blockade was clearly use dependent, whereas this was not the case for either Pb2+ or Zn2+ The blockade by none of these metals was totally reversible. The best recovery was obtained upon wash after exposure to Pb2+ (greater than or equal to 60%), some recovery was seen with Zn2+ (greater than or equal to 50%), but there was little or no recovery after application of Al3+. With Zn2+ or Al3+ in the external solution the current-voltage relation often shifted to depolarized voltages. The degree of the shift was a function of concentration, but differed from cell to cell and was probably because of a charge-screening action. The actions of Pb2+ and Al3+ are relatively specific for voltage-activated calcium channels. Concentrations that block the voltage-activated calcium channel currents by >80% (I mu M Pb2+ or 200 mu M Al3+) had little effect (<20%) on voltage-activated potassium or sodium channel currents. The effects of Zn2+ were less specific.