Developmental Effects of Chronic Low-Level Lead Exposure on Voltage-Gated Calcium Channels in Brain Synaptosomes Obtained from the Neonatal and the Adult Rats

Abstract

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 Ca 2+ influx channels (VGCCs), and (2) the depolarization-induced rise in [Ca 2+] 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 [Ca 2+] i in both the neonatal and the adult samples. The depolarization-induced increase in [Ca 2+] 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 [Ca 2+] 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 lead 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.