Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular free Ca2+ in cultured rat hippocampal neurons.
OBJECTIVE
To examine the effects of Pb2+ on N-methyl-D-aspartate (NMDA)-, K(+)- and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration ([Ca2+]i) in cultured fetal rat hippocampal neurons in order to explain the cognitive and learning deficits produced by this heavy metal.


METHODS
Laser scanning confocal microscopy was used.


RESULTS
The results clearly demonstrated that adding Pb2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca2+]i in a concentration-dependent manner. In contrast, Pb2+ treatment did not markedly affect increases in [Ca2+]i induced by an admixture of QA and KA. The minimal inhibitory effect of Pb2+ occurred at 1 mumol/L, and more than seventy percent abolition of the NMDA-stimulated increase in [Ca2+]i was observed at 100 mumol/L Pb2+. Evaluation of Pb(2+)-induced increase in [Ca2+]i response to elevating extracellular concentrations of NMDA, glycine or calcium revealed that Pb2+ was a noncompetitive antagonist of both NMDA and glycine, and a competitive antagonist of Ca2+ at NMDA receptor channels. In addition, Pb2+ inhibited depolarization-evoked increases in [Ca2+]i mediated by K+ stimulation (30 mumol/L), indicating that Pb2+ also depressed the voltage-dependent calcium channels. Also, the results showed that Pb2+ appeared to be able to elevate the resting levels of [Ca2+]i in cultured neurons, implying a reason for Pb(2+)-enhanced spontaneous release of several neurotransmitters reported in several previous studies.


CONCLUSIONS
Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular [Ca2+]i in cultured hippocampal neurons.
Zhang
Heng-Shan
HS
Department of Toxicology, Institute of Environmental Health Monitoring, Chinese Academy of Preventive Medicine, 7 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.
Song
Li-Hua
LH
Wang
Li
L
Qin
Yu-Hui
YH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology*; D007854:Lead / Q000009:adverse effects*; D007859:Learning Disabilities / Q000139:chemically induced*; D018613:Microscopy, Confocal; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D007854:Lead; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium