QUISQUALATE METABOTROPIC RECEPTORS MODULATE NMDA CURRENTS AND FACILITATE INDUCTION OF LONG-TERM POTENTIATION THROUGH PROTEIN-KINASE-C
QUISQUALATE METABOTROPIC RECEPTORS MODULATE NMDA CURRENTS AND FACILITATE INDUCTION OF LONG-TERM POTENTIATION THROUGH PROTEIN-KINASE-C
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DOI：
10.1111/j.1460-9568.1992.tb00900.x
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发表时间：
1992-06-01
影响因子：
3.4
通讯作者：
BENARI, Y
中科院分区：
文献类型：
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作者：
ANIKSZTEJN, L;OTANI, S;BENARI, Y
在大鼠海马脑片上，采用细胞内和细胞外记录方法，研究了使君子酸代谢型受体（Q（p））与N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）介导的电流之间的相互作用。我们发现trans-ACPD和1 S，3R-ACPD增强NMDA介导的电流，但不增强AMPA介导的电流。选择性蛋白激酶C抑制剂的细胞内注射阻止了NMDA反应的上调。通过ACPD上调NMDA反应对长时程增强诱导阈值的生理后果进行了测试。我们发现，产生短时程增强的阈下电刺激产生长时程增强时，再加上ACPD的应用，这是不是AMPA或NMDA产生的效果。这种作用被蛋白激酶C抑制剂阻断。这些结果首次证明了一种谷氨酸受体亚型（Q（p））可以通过激活蛋白激酶C来调节另一种谷氨酸受体亚型（NMDA）。我们的研究结果还表明，NMDA受体的调节蛋白激酶C，和蛋白激酶C的细胞内水平可能决定的阈值诱导的长时程增强。
Using intracellular and extracellular recordings in rat hippocampal slices, we have investigated the interactions between the quisqualate metabotropic receptor (Q(p)) and currents mediated by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). We found that trans-(t)-l-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) and 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (lS,3R-ACPD) potentiated NMDA but not AMPA-mediated currents. Intracellular injections of selective protein kinase C inhibitors prevented the up-regulation of the NMDA response. The physiological consequence of the up-regulation by ACPD of the NMDA response on the threshold of long-term potentiation induction was tested. We found that a subthreshold train of electrical stimulation that produced short-term potentiation generated long-term potentiation when coupled with ACPD application, an effect which was not produced by AMPA or NMDA. This effect was blocked by an inhibitor of protein kinase C. These results demonstrate for the first time that one subtype of glutamate receptor (Q(p)) can regulate another subtype of glutamate receptor (NMDA) through the activation of protein kinase C. Our results also suggest that the NMDA receptor is regulated by protein kinase C, and that the intracellular level of protein kinase C may determine the threshold for induction of long-term potentiation.