Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex.
Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex.
复制标题
大鼠前额皮质 I 层神经元烟碱乙酰胆碱受体对 AMPA 受体介导的电流的调节。
DOI：
10.1038/srep14099
复制
发表时间：
2015-09-15
影响因子：
4.6
通讯作者：
Chen GJ
中科院分区：
文献类型：
--
作者：
Tang B;Luo D;Yang J;Xu XY;Zhu BL;Wang XF;Yan Z;Chen GJ
前额叶皮层（PFC）的第一层神经元与深层神经元具有广泛的突触连接，这表明它们在神经回路中起着重要作用。研究表明，烟碱乙酰胆碱受体（nAChRs）的激活增加了这一层的兴奋性神经传递。本研究发现，尼古丁选择性地增加了AMPA受体（AMPAR）介导的电流振幅和AMPA/NMDA比值，而对NMDA受体介导的电流没有影响。选择性α - 7- nachr拮抗剂甲基莱卡乌碱（MLA）和细胞内钙螯合剂BAPTA抑制尼古丁对AMPAR电流的增强。此外，MLA还能抑制mEPSC或配对脉冲比的烟碱效应。此外，尼古丁增强了AMPAR电流的内向整流，表明钙透性和含有GluA1的AMPAR具有功能作用。一致地，尼古丁增强的AMPAR电流被选择性钙透性AMPAR抑制剂IEM-1460所抑制。最后，在CAMKII、PKC或PKA磷酸化位点合成肽阻断AMPAR的GluA1亚基，以及相应的激酶抑制剂，阻断烟碱对AMPA/NMDA比值的增加。这些结果表明尼古丁通过调节依赖于α7-nAChR和细胞内钙的GluA1磷酸化状态来增加AMPAR电流。
Layer I neurons in the prefrontal cortex (PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors (nAChRs) increases excitatory neurotransmission in this layer. Here we found that nicotine selectively increased the amplitude of AMPA receptor (AMPAR)-mediated current and AMPA/NMDA ratio, while without effect on NMDA receptor-mediated current. The augmentation of AMPAR current by nicotine was inhibited by a selective α7-nAChR antagonist methyllycaconitine (MLA) and intracellular calcium chelator BAPTA. In addition, nicotinic effect on mEPSC or paired-pulse ratio was also prevented by MLA. Moreover, an enhanced inward rectification of AMPAR current by nicotine suggested a functional role of calcium permeable and GluA1 containing AMPAR. Consistently, nicotine enhancement of AMPAR current was inhibited by a selective calcium-permeable AMPAR inhibitor IEM-1460. Finally, the intracellular inclusion of synthetic peptide designed to block GluA1 subunit of AMPAR at CAMKII, PKC or PKA phosphorylation site, as well as corresponding kinase inhibitor, blocked nicotinic augmentation of AMPA/NMDA ratio. These results have revealed that nicotine increases AMPAR current by modulating the phosphorylation state of GluA1 which is dependent on α7-nAChR and intracellular calcium.