Differential effects of zinc influx via AMPA/kainate receptor activation on subsequent induction of hippocampal CA1 LTP components
Differential effects of zinc influx via AMPA/kainate receptor activation on subsequent induction of hippocampal CA1 LTP components
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DOI：
10.1016/j.brainres.2010.07.039
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发表时间：
2010-10
期刊：
影响因子：
2.9
通讯作者：
A. Takeda;Miki Suzuki;Haruna Tamano;M. Ando;N. Oku
中科院分区：
文献类型：
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作者：
A. Takeda;Miki Suzuki;Haruna Tamano;M. Ando;N. Oku
低微摩尔浓度的锌可增强NMDA受体依赖的海马CA 1区长时程增强（LTP）的诱导，而过量的锌则减弱LTP的诱导，突触锌的稳态对LTP的诱导至关重要。本研究以幼年大鼠海马脑片为材料，研究了锌离子进入海马细胞的时间和水平对海马CA 1区突触LTP的影响。锌（100μM）灌流可增加细胞内锌水平，并减弱强直刺激（100 Hz，1 s）引起的CA 1 LTP，此作用可被NMDA受体拮抗剂APV（50μM）完全抑制。在锌灌注前灌注10μ MCNQX（一种AMPA/红藻氨酸受体拮抗剂）可减少锌内流至海马细胞，使锌灌注引起的CA 1 LTP衰减恢复。这些结果表明，促进锌流入海马细胞通过AMPA/红藻氨酸受体激活是一个事件，以减弱随后的诱导NMDA受体依赖的CA 1 LTP。另一方面，锌预灌注也减弱了200-Hz强直刺激诱导的海马CA 1区LTP，但在APV存在下，对200-Hz强直刺激诱导的NMDA受体非依赖性CA 1区LTP无影响，提示NMDA受体非依赖性CA 1区LTP的诱导对易化锌内流的敏感性降低。锌内流通过AMPA/红藻氨酸受体激活可能差异作用于随后的诱导CA 1 LTP组件。
Zinc potentiates the induction of NMDA receptor-dependent hippocampal CA1 long-term potentiation (LTP) at low micromolar concentrations, while excessive zinc attenuates it. Homeostasis of synaptic zinc is critical for LTP induction. In the present study, LTP at hippocampal CA1 synapses was analyzed focused on the timing and level of zinc influx into hippocampal cells in hippocampal slices from young rats. Zinc (100μM) perfusion increased intracellular zinc level and subsequently attenuated CA1 LTP induced by tetanic stimuli at 100 Hz for 1s, which was completely inhibited in the presence of 50μM APV, an NMDA receptor antagonist. When 10μM CNQX, an AMPA/kainate receptor antagonist, which reduced zinc influx into hippocampal cells, was perfused prior to the zinc perfusion, the attenuation of CA1 LTP by the zinc perfusion was restored. These results suggest that facilitated zinc influx into hippocampal cells via AMPA/kainate receptor activation is an event to attenuate subsequent induction of NMDA receptor-dependent CA1 LTP. On the other hand, the zinc pre-perfusion also attenuated CA1 LTP induced by 200-Hz tetanus, but not NMDA receptor-independent CA1 LTP induced by 200-Hz tetanus in the presence of APV, suggesting that the induction of NMDA receptor-independent CA1 LTP is less susceptibility to the facilitated zinc influx into hippocampal CA1 cells. Zinc influx via AMPA/kainate receptor activation may differentially act on subsequent induction of CA1 LTP components.