Developmental effects of chronic low-level lead exposure on voltage-gated calcium channels in brain synaptosomes obtained from the neonatal and the adult rats

Effects of chronic low level (1 mg/kg/day) lead exposure were studied on (1) the density and the binding properties of L, N, and P type voltage gated Ca²⁺ influx channels (VGCCs), and (2) the depolarization induced rise in [Ca²⁺](i) in synaptosomes obtained from the brains of the neonatal (postnatal-day-5) and the adult (postnatal-week 20) rats. Lead exposure started prenatally and continued for either up to postnatal-day-5 or up to postnatal-week-20. The K(D) and the B(max) values for the binding of nifedipine (antagonist of L type channels), ω-CgTx (a specific antagonist of N type channels) and ω-AgaTx (antagonist of P type channels) to VGCCs in the neonatal samples were less then those in the adult samples. Depolarization increased (1) the density and the antagonist binding affinity of VGCCs and (2) increased [Ca²⁺](i) in both the neonatal and the adult samples. The depolarization-induced increase in [Ca²⁺](i) in the neonatal samples was lower than that in the adult samples. Chronic low-level lead exposure decreased the densities of L, N, and P type VGCCs and attenuated the depolarization-induced increase in [Ca²⁺](i) in synaptosomes. Chronic low-level lead exposure, however, did not affect the relative ratio of L, N, and P channels, the affinity of VGCCs for antagonists, and the depolarization induced increase in antagonist binding to VGCCs in synaptosomes. Thus chronic low-level lend exposure during early development and adulthood may decrease the synthesis of VGCCs but not their antagonist binding affinity in both the neonatal and the adult rats.