Orexin-B modulates synaptic transmission of rod bipolar cells in rat retina
Orexin-B modulates synaptic transmission of rod bipolar cells in rat retina
复制标题
Orexin-B 调节大鼠视网膜杆状双极细胞的突触传递
DOI：
10.1016/j.neuropharm.2018.01.007
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发表时间：
2018-05-01
影响因子：
4.7
通讯作者：
Zhong, Yong-Mei
中科院分区：
文献类型：
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作者：
Zhang, Gong;Wu, Xiao-Hua;Zhong, Yong-Mei
食欲素-A、B通过激活两个G蛋白偶联受体：食欲素受体1(OX1R)和食欲素受体2(OX2R)，在觉醒和摄食过程中发挥重要作用。增食欲素和增食欲素受体在视网膜神经元中表达，它们被证明对视网膜内无长突细胞和神经节细胞的兴奋性AMPA受体有不同的调节作用。在这项工作中，我们报道了食欲素-B调节位于大鼠视网膜外的视杆双极细胞(RBC)的活动。玻璃体内注射增食欲素-B可增加活体记录的暗视视网膜电图b波的幅度，这反映了红细胞的活性。在大鼠视网膜切片上的膜片钳记录显示，增食欲素-B不改变光感受器驱动的红细胞反应中的谷氨酸能兴奋成分。观察增食欲素B对GABA受体介导的红细胞突触传递的影响。在视网膜切片制备中，食欲素-B抑制GABA受体介导的内网状层红细胞的抑制性突触后电流。此外，在分离的红细胞上的全细胞记录表明，食欲素-B抑制GABA(C)受体，但不抑制GABA(A)受体介导的红细胞电流，这一作用可被OX1R和OX2R拮抗剂阻断。食欲素-B对GABA(C)电流的抑制作用可能是通过G(I/o)/PC-PLOCa~(2+)非依赖的PKC信号通路实现的，当分别用Gdp-β-S/百日咳毒素(针对G(I/o))、D609(针对PLC)、双吲哚马来酰亚胺(针对PKC)/rotlerin(针对PKC Delta)阻断上述通路的每一步时，这种抑制作用是不存在的。增食欲素-B诱导的红细胞活性增强可改善动物在暗期(觉醒期)的视力和对比敏感度。(C)2018爱思唯尔有限公司。保留所有权利。
Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo. Patch clamp recordings in rat retinal slices showed that orexin-B did not change glutamatergic excitatory component of the RBC response driven by photoreceptors. Effects of orexin-B on GABA receptor-mediated synaptic transmission of RBCs were then examined. In retinal slice preparations orexin-B suppressed GABA receptor-mediated inhibitory postsynaptic currents of RBCs in the inner plexiform layer. Furthermore, using whole-cell recordings in isolated RBCs it was shown that orexin-B suppressed GABA(C) receptor-, but not GABA(A) receptor-, mediated currents of the RBCs, an effect that was blocked by OX1R and OX2R antagonists. The orexin-B-induced inhibition of GABA(C) currents was likely mediated by a G(i/o)/PC-PLOCa2+-independent PKC signaling pathway, as such inhibition was absent when each step of the above-pathway was blocked with GDP-beta-S/pertussis toxin (for G(i/o)), D609 (for PLC), bisindolylmaleimide IV (for PKC)/rottlerin (for PKC delta), respectively. The orexin-B-induced potentiation of RBC activity may improve visual acuity and contrast sensitivity of the animal during the dark period (wake phase). (C) 2018 Elsevier Ltd. All rights reserved.