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 M. More than 80% of the calcium entry was prevented by 5 M lead. The IC₅₀ and the Hill coefficient were 1.3 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 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.