Lead inhibited N-methyl-D-aspartate receptor-independent long-term potentiation involved ryanodine-sensitive calcium stores in rat hippocampal area CA1.
Lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term potentiation (LTP) has been reported in area CA1 of rat hippocampus following lead exposure in vivo and in vitro. The present study was carried out to investigate whether the alterations of N-methyl-d-aspartate (NMDA) receptor-independent LTP following lead exposure involve internal calcium stores in hippocampus CA1 synapses. Monosynaptic field excitatory postsynaptic potentials in hippocampal slice area CA1 were recorded using the whole-cell patch-clamp upon acute lead treatment, and these studies were coupled with calcium imaging experiments to observe internal calcium changes in cultured hippocampal neurons. Inhibiting calcium release by ryanodine significantly reduced NMDA receptor-independent LTP, and depletion of internal calcium stores with thapsigargin blocked this form of LTP. Caffeine, an agonist of ryanodine receptors, enhanced this form of LTP. However, caffeine-enhanced NMDA receptor-independent LTP was depressed after bath application of lead. Moreover, lead further decreased ryanodine- and thapsigargin-reduced NMDA receptor-independent LTP. Calcium imaging also confirmed that lead had an effect on internal calcium release and uptake. Taken together, these results demonstrated that lead inhibited NMDA receptor-independent LTP by action on calcium release and uptake by ryanodine-sensitive stores in rat hippocampal area CA1.
Li
X M
XM
School of Life Sciences and Institute of Polar Environment, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Gu
Y
Y
She
J Q
JQ
Zhu
D M
DM
Niu
Z D
ZD
Wang
M
M
Chen
J T
JT
Sun
L G
LG
Ruan
D-Y
DY
D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012433:Ryanodine / Q000819:agonists / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014966:Xanthenes
D000814:Aniline Compounds; D004791:Enzyme Inhibitors; C409648:Fluo 4; D016194:Receptors, N-Methyl-D-Aspartate; D014966:Xanthenes; D012433:Ryanodine; D007854:Lead; D002110:Caffeine; D019284:Thapsigargin; D002118:Calcium