Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex
Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex
复制标题
DOI：
10.1073/pnas.0308618100
复制
发表时间：
2004-02-24
影响因子：
11.1
通讯作者：
Yan, Z
中科院分区：
文献类型：
--
作者：
Chen, GJ;Greengard, P;Yan, Z
多巴胺与前额皮质（PFC）和其他脑区n -甲基- d -天冬氨酸受体（NMDARs）之间的相互作用被认为在正常的心理功能和神经精神疾病中起着重要作用。在这项研究中，我们研究了多巴胺D-1受体对PFC锥体神经元NMDAR电流的调节。应用D-1受体激动剂SKF81297引起急性分离PFC锥体神经元稳态nmda诱发电流显著增加。D-1对NMDARs的影响不依赖于蛋白激酶A或蛋白磷酸酶1，但在无Ca2+培养基中培养神经元可以消除D-1对NMDARs的影响。细胞内应用Ca2+螯合剂、钙调素或钙调素抑制剂在很大程度上阻止了NMDAR电流的D调制。此外，抑制PKC活性或破坏PKC与其锚定蛋白的结合也显著降低了D-1对NMDAR电流的影响。多巴胺D-1受体对NMDAR活性的上调，以及之前关于NMDAR激活上调多巴胺D-1受体的发现，为D-1与NMDAR相互作用提供了一种细胞机制。这些相互作用可能在调节突触可塑性，从而在认知和情绪过程中发挥重要作用。
Interactions between dopamine and N-methyl-D-aspartate receptors (NMDARs) in prefrontal cortex (PFC) and other brain regions are believed to play an important role in normal mental function and neuropsychiatric disorders. In this study, we examined the regulation of NMDAR currents by the dopamine D-1 receptor in PFC pyramidal neurons. Application of the D-1 receptor agonist SKF81297 caused a prominent increase of the steady-state NMDA-evoked current in acutely isolated PFC pyramidal neurons. The D-1 effect on NMDARs was independent of protein kinase A or protein phosphatase 1, but was abolished by incubation of neurons in Ca2+-free medium. Intracellular application of the Ca2+ chelator, calmodulin, or calmodulin inhibitors largely prevented the D, modulation of NMDAR currents. Moreover, inhibiting PKC activity or disrupting PKC association with its anchoring protein also significantly reduced the D-1 effect on NMDAR currents. This upregulation of NMDAR activity by dopamine D-1 receptors and the previous finding on up-regulation of dopamine D-1 receptors by NMDAR activation provide a cellular mechanism for the reciprocal interactions between D-1 and NMDARs. These interactions may play an important role in modulating synaptic plasticity and thus in cognitive and emotional processes.