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 KD and the Bmax values for the binding of nifedipine (antagonist of L type channels), omega-CgTx (a specific antagonist of N type channels) and omega-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 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.
Singh
A K
AK
Minnesota Veterinary Diagnostic Laboratory, Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA.
Jiang
Y
Y
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects*; D007855:Lead Poisoning / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009543:Nifedipine