Lead reduces depolarization-induced calcium entry in cultured DRG neurons without crossing the cell membrane: Fura-2 measurements

1. Cultured dorsal root ganglion neurons of rat pups were depolarized by exposure to 50 mM K+ and the rise of [Ca2(+)](i) was measured using fura-2 as an indicator. 2. Lead in the extracellular solution reduced the rise of [Ca2+](i) in a concentration-dependent manner, with a threshold concentration of 0.25 mu M. More than 80% of the calcium entry was prevented by approximate to 5 mu M lead. The IC50 and the Hill coefficient were 1.3 mu M and 1, respectively. 3. This effect was considered to be due to a reduction of VACCCs, since applications of NMDA did not result in any rise of [Ca2+](i). 4. Since Pb2+ itself changes the fura-2 signal in a typical and characteristic manner, fura-2 is also an indicator for Pb2+, No changes in fura-2 signals were detected when lead (5 mu M) was applied for several minutes in the absence of calcium, indicating that Pb2+ did not enter the cells. 5. Thus it is concluded that lead prevents calcium entry by reducing VACCCs but does not cross the cell membrane itself.