Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Global COE, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Brain Res. 2010 Apr 6;1323:59-64. doi: 10.1016/j.brainres.2010.01.085. Epub 2010 Feb 6.
Long-term potentiation (LTP) at hippocampal CA1 synapses consists of N-methyl-d-aspartate (NMDA) receptor-dependent and NMDA receptor-independent forms. The action of divalent heavy metals, which are NMDA receptor antagonists, was examined focusing on the evidence that CA1 LTP induced by a 100-Hz tetanus for 1s is abolished in the presence of 2-amino-5-phosphonovalerate (APV), a NMDA receptor antagonist. Only ZnCl2 (5microM) of heavy metals tested potentiated CA1 LTP. CA1 LTP induced by repeated 100-Hz tetanus (1s, 6 times, 10min interval), which reached a plateau in magnitude, was abolished in the presence of 50microM APV. In this case, CA1 LTP after the first tetanus was potentiated in the presence of 5microM ZnCl2, whereas CA1 LTP after the last tetanus was not potentiated. These results indicate that the magnitude of NMDA receptor-dependent CA1 LTP can be positively shifted with 5microM ZnCl2 in the range of the maximum magnitude. CA1 LTP induced by a 200-Hz tetanus for 1s was not potentiated in the presence of 5microM ZnCl2 and was partially inhibited in the presence of APV. Furthermore, CA1 LTP induced by a 200-Hz tetanus for 1s in the presence of APV was not potentiated in the presence of 5microM ZnCl2, indicating that NMDA receptor-independent CA1 LTP is not potentiated with 5microM ZnCl2. The present study suggests that zinc differentially acts on CA1 LTP components.
长时程增强（LTP）在海马 CA1 突触包括 N-甲基-D-天冬氨酸（NMDA）受体依赖性和 NMDA 受体非依赖性形式。二价重金属的作用，作为 NMDA 受体拮抗剂，被检查集中在证据表明，由 100-Hz 强直刺激 1s 诱导的 CA1 LTP 在 NMDA 受体拮抗剂 2-氨基-5-磷戊酸（APV）存在时被消除。只有测试的重金属 ZnCl2（5μM）增强 CA1 LTP。由重复 100-Hz 强直刺激（1s，6 次，10min 间隔）诱导的 CA1 LTP，其幅度达到平台，在 50μM APV 存在时被消除。在这种情况下，在 5μM ZnCl2 存在下，第一次强直刺激后的 CA1 LTP 被增强，而最后一次强直刺激后的 CA1 LTP 没有被增强。这些结果表明，NMDA 受体依赖性 CA1 LTP 的幅度可以在最大幅度的范围内用 5μM ZnCl2 正向移动。在 5μM ZnCl2 存在下，由 100-Hz 强直刺激 1s 诱导的 CA1 LTP 没有被增强，并且在 APV 存在下部分抑制。此外，在 APV 存在下，由 100-Hz 强直刺激 1s 诱导的 CA1 LTP 没有在 5μM ZnCl2 存在下被增强，表明 NMDA 受体非依赖性 CA1 LTP 没有被 5μM ZnCl2 增强。本研究表明锌对 CA1 LTP 成分的作用不同。
