Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular free Ca2+ in cultured rat hippocampal neurons / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences
; (12): 330-340, 2002.
Article
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| ID: wpr-264302
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ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>Laser scanning confocal microscopy was used.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular [Ca2+]i in cultured hippocampal neurons.</p>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Pharmacologie
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Physiologie
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Potassium
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Calcium
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N-Méthyl-aspartate
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Acide quisqualique
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Rat Wistar
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Troubles de la cognition
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Microscopie confocale
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Modèles animaux de maladie humaine
Type d'étude:
Prognostic_studies
Limites du sujet:
Animals
langue:
En
Texte intégral:
Biomedical and Environmental Sciences
Année:
2002
Type:
Article