Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE-21, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Brain Res. 2010 Oct 1;1354:188-95. doi: 10.1016/j.brainres.2010.07.039. Epub 2010 Jul 21.
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 (100 microM) 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 50 microM APV, an NMDA receptor antagonist. When 10 microM 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.
锌在低微摩尔浓度下增强 NMDA 受体依赖性海马 CA1 长时程增强（LTP）的诱导，而过量的锌则会减弱它。突触锌的稳态对于 LTP 的诱导至关重要。在本研究中，我们分析了年轻大鼠海马切片中海马 CA1 突触的 LTP，重点关注锌流入海马细胞的时间和水平。100μM 的锌灌注会增加细胞内锌水平，随后减弱 100Hz 刺激 1s 诱导的 CA1 LTP，而在存在 NMDA 受体拮抗剂 50μM APV 的情况下，这种减弱完全被抑制。当在锌灌注之前灌注 10μM 的 CNQX（一种 AMPA/kainate 受体拮抗剂）以减少锌流入海马细胞时，锌灌注对 CA1 LTP 的减弱作用得到恢复。这些结果表明，通过 AMPA/kainate 受体激活促进锌流入海马细胞是减弱随后 NMDA 受体依赖性 CA1 LTP 诱导的事件。另一方面，锌预灌注也减弱了由 200Hz 强直刺激诱导的 CA1 LTP，但不能减弱在 APV 存在下由 200Hz 强直刺激诱导的 NMDA 受体非依赖性 CA1 LTP，这表明 NMDA 受体非依赖性 CA1 LTP 的诱导对促进锌流入海马 CA1 细胞的敏感性较低。通过 AMPA/kainate 受体激活的锌内流可能对随后的 CA1 LTP 诱导成分产生不同的作用。
