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 microM, compared to an IC50 of 2.2 microM for Cd2+. The current activated by a depolarization from -40 to 0 mV was inhibited by 50% by 1.0 microM Pb2+. Low threshold currents activated by a step from -100 to -30 mV were blocked by Pb2+ at higher concentrations (IC50 = 6 microM). The block progressed in the absence of channel activation and showed little voltage dependence. Peak sodium current was reduced by 6.6% at 1 microM Pb2+ while at 20 microM 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 microM Pb2+. Thus, Pb2+ selectively blocks calcium currents at concentrations in the range of those causing toxicity in man.
Evans
M L
ML
Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany 12201-0509.
Büsselberg
D
D
Carpenter
D O
DO
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D020960:omega-Conotoxins
D015220:Calcium Channels; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D007854:Lead; D009553:Nimodipine; D011493:Protein Kinase C