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代谢型谷氨酸受体参与大鼠海马中钙诱导的AMPA和NMDA受体介导反应的长时程增强。

Metabotropic glutamate receptors are involved in calcium-induced LTP of AMPA and NMDA receptor-mediated responses in the rat hippocampus.

作者信息

Yang S N, Wu J N, Liu D, Tung C S

机构信息

Department of Physiology, National Defense Medical Center, Taipei, Taiwan, ROC.

出版信息

Brain Res Bull. 1998 Aug;46(6):505-12. doi: 10.1016/s0361-9230(98)00046-x.

DOI:10.1016/s0361-9230(98)00046-x
PMID:9744287
Abstract

Effects of metabotropic glutamate (mGlu) receptors on calcium-induced long-term potentiation (LTP) of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components were investigated in rat hippocampal slices using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs). Calcium-induced LTP comprises a parallel, long-lasting increase of AMPA and NMDA receptor-mediated components. The calcium-induced LTP of the AMPA receptor-mediated component can be significantly attenuated by the use of a selective NMDA antagonist. (R.S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a selective antagonist of mGlu receptors, abolished the long-lasting increase of both AMPA and NMDA receptor-mediated components observed in calcium-induced LTP. In current clamp mode, the application of a high calcium alone or Schaffer fiber stimulation alone (20 Hz) only generated a short-term increase in the firing rate of evoked action potentials. Conversely, a long-term increase in the firing rate was observed if Schaffer fiber stimulation (20 Hz) accompanied the perfusion of high calcium. These results suggest that calcium-induced LTP involves a parallel, long-lasting enhancement in ionotropic AMPA and NMDA receptor-mediated components. More importantly, the mGlu receptor plays a critical role in the establishment of both AMPA and NMDA receptor-mediated components underlying calcium-induced LTP. In addition, the present study also described an experimental condition in which the coapplication of the high calcium pulse and Schaffer fiber stimulation (20 Hz) can synergistically elicit a long-term increase of neuronal excitability.

摘要

使用全细胞膜片钳记录兴奋性突触后电流(EPSC),在大鼠海马切片中研究了代谢型谷氨酸(mGlu)受体对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和N-甲基-D-天冬氨酸(NMDA)受体介导成分的钙诱导长时程增强(LTP)的影响。钙诱导的LTP包括AMPA和NMDA受体介导成分的平行、持久增加。AMPA受体介导成分的钙诱导LTP可通过使用选择性NMDA拮抗剂而显著减弱。(R.S)-α-甲基-4-羧基苯甘氨酸(MCPG),一种mGlu受体的选择性拮抗剂,消除了在钙诱导LTP中观察到的AMPA和NMDA受体介导成分的持久增加。在电流钳模式下,单独应用高钙或单独进行Schaffer纤维刺激(20Hz)仅引起诱发动作电位发放率的短期增加。相反,如果Schaffer纤维刺激(20Hz)伴随着高钙灌注,则观察到发放率的长期增加。这些结果表明,钙诱导的LTP涉及离子型AMPA和NMDA受体介导成分的平行、持久增强。更重要的是,mGlu受体在钙诱导LTP的AMPA和NMDA受体介导成分的建立中起关键作用。此外,本研究还描述了一种实验条件,即高钙脉冲和Schaffer纤维刺激(20Hz)共同应用可协同引起神经元兴奋性的长期增加。

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