ACTIVATION OF DOPAMINE D1 RECEPTORS ENHANCES THE TEMPORAL SUMMATION AND EXCITABILITY OF RAT RETINAL GANGLION CELLS
ACTIVATION OF DOPAMINE D1 RECEPTORS ENHANCES THE TEMPORAL SUMMATION AND EXCITABILITY OF RAT RETINAL GANGLION CELLS
复制标题
多巴胺 D1 受体的激活增强大鼠视网膜神经节细胞的时间总和和兴奋性。
DOI：
10.1016/j.neuroscience.2017.04.046
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发表时间：
2017-07-04
期刊：
影响因子：
3.3
通讯作者：
Wang, Zhongfeng
中科院分区：
文献类型：
--
作者：
Cui, Peng;Li, Xue-Yan;Wang, Zhongfeng
多巴胺(DA)是一种重要的神经递质和神经调节剂，通过激活G蛋白偶联的DA_1和/或DA_2受体，在神经元的生理功能中发挥重要作用。以往的研究表明，D1受体在视网膜神经元和包括神经节细胞在内的神经胶质细胞中有功能表达。在本研究中，我们利用电生理技术探讨了D1R的激活对大鼠视网膜脑片视网膜神经节细胞(RGC)时间总和和兴奋性的影响。选择性D_1受体激动剂SKF81297可增加刺激序列(5个40赫兹电流脉冲)诱发的兴奋性突触后电位(EPSP)的比值(EPSP5/EPSP1)，此作用可被特异性D_1受体拮抗剂SCH23390阻断。内向整流性钾通道(KIR)阻断剂Ba2+可显著抑制SKF81297的作用，而超极化激活的阳离子电流(I-h)阻断剂ZD7288对SKF81297的抑制作用中等。在SKF81297诱导的EPSP时间总和的调节中，cAMP/蛋白激酶A(PKA)信号通路，而不是磷脂酶C(PI-PLC)介导。进一步的实验表明，SKF81297抑制视网膜神经节细胞Ba2+敏感的KIR电流。此外，SKF81297增加视网膜节细胞的自发放电频率，并在突触受体阻滞剂存在或不存在的情况下引起细胞的去极化。SKF81297对RGCs记录的微小兴奋性突触后电流(MEPSCs)频率无明显影响。我们的结果表明，D1R的激活主要通过cAMP/PKA信号通路抑制KIR电流，从而增强RGCs的兴奋性，从而增强RGCs的时间总和。(C)2017年IBRO。爱思唯尔有限公司出版。保留所有权利。
Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques. Bath application of the selective D1 receptor agonist SKF81297 increased the ratio of excitatory postsynaptic potentials (EPSPs) (EPSP5/EPSP1) within an EPSP train evoked by a train stimulation (five current pulses at 40 Hz), which was blocked by co-application of SCH23390, a specific D1 receptor antagonist. Ba2+, an inwardly rectifying K+ channel (Kir) blocker, significantly suppressed the SKF81297-induced effect, whereas ZD7288, a specific hyperpolarization-activated cation current (I-h) blocker, showed a moderate inhibitory effect. The cAMP/protein kinase A (PKA) signaling pathway, but not phosphoinositide-specific phospholipase C (PI-PLC), mediated the SKF81297-induced modulation of EPSP temporal summation. Further experiments showed that SKF81297 suppressed Ba2+-sensitive Kir currents in RGCs. Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and caused depolarization of the cells with or without the presence of synaptic receptor blockers. In contrast, SKF81297 did not significantly change the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in RGCs. Our results indicate that D1 receptor activation enhances the temporal summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA signaling pathway, thus increasing the excitability of rat RGCs. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.