PB2+ BLOCKS CALCIUM CURRENTS OF CULTURED DORSAL-ROOT GANGLION-CELLS

The divalent cation lead (Pb2+) blocks sustained and transient voltage sensitive calcium channel currents of cultured rat dorsal root ganglion cells. The IC50 for inhibition of the total peak current evoked by a step depolarization from -80 to 0 mV was 0.6-mu-M, compared to an IC50 of 2.2-mu-M for Cd2+. The current activated by a depolarization from -40 to 0 mV was inhibited by 50% by 1.0-mu-M Pb2+. Low threshold currents activated by a step from -100 to -30 mV were blocked by Pb2+ at higher concentrations (IC50 = 6-mu-M). The block progressed in the absence of channel activation and showed little voltage dependence. Peak sodium current was reduced by 6.6% at 1-mu-M Pb2+ while at 20-mu-M the peak current was reduced by 40% with marked slowing of the time course of activation. The potassium rectifier current was reduced by 4.1% at 1-mu-M Pb2+. Thus, Pb2+ selectively blocks calcium currents at concentrations in the range of those causing toxicity in man.