Orexin-A differentially modulates AMPA-preferring responses of ganglion cells and amacrine cells in rat retina
Orexin-A differentially modulates AMPA-preferring responses of ganglion cells and amacrine cells in rat retina
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Orexin-A 差异调节大鼠视网膜神经节细胞和无长突细胞的 AMPA 偏好反应
DOI：
10.1016/j.neuropharm.2015.01.016
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发表时间：
2015-06
影响因子：
4.7
通讯作者：
Zhong Yong Mei
中科院分区：
文献类型：
--
作者：
Zheng Chao;Deng Qin Qin;Liu Lei Lei;Wang Meng Ya;Zhang Gong;Sheng Wen Long;Weng Shi Jun;Yang Xiong Li;Zhong Yong Mei
通过激活它们的受体（OX 1 R和OX 2 R）食欲素-A/B调节清醒/睡眠状态、进食行为，但是这些肽在视网膜中的功能仍然未知。采用大鼠离体视网膜细胞膜片钳记录和钙离子成像技术，我们证实orexin-A通过OX 1 R抑制神经节细胞（GC）的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）偏好性受体介导的电流（AMPA偏好性电流），但通过OX 2 R增强无长突细胞（AC）的AMPA偏好性电流。一致的，在大鼠视网膜切片orexin-A抑制光诱发的AMPA偏好受体介导的兴奋性突触后电流的GC，但增强那些在AC。胞内透析GDP-β-S或用Gi/o抑制剂百日咳毒素（PTX）预孵育可消除这两种作用。cAMP/蛋白激酶A（PKA）抑制剂Rp-cAMP或cGMP/PKG阻断剂KT 5823均不能改变食欲素-A的作用。虽然它们都涉及蛋白激酶C（PKC）的激活，但对GC和AC的影响分别被磷脂酰肌醇（PI）-磷脂酶C（PLC）抑制剂和磷脂酰胆碱（PC）-PLC抑制剂消除。此外，在GC中，食欲素-A增加[Ca ~（2+）] i，并且食欲素-A的作用被细胞内无Ca ~（2+）溶液和肌醇1，4，5-三磷酸（IP_3）受体拮抗剂阻断。与此相反，orexin-A没有改变[Ca 2 +] i在AC和orexin-A的效果仍然在细胞内或细胞外的Ca 2 +-自由的溶液。OX 1 R激活后，Orexin-A对GC的作用可能是由一条独特的Gi/o/PI-PLC/IP 3/Ca 2+依赖性PKC信号通路介导的，而OX 2 R激活后，一条Gi/o/PC-PLC/Ca 2+非依赖性PKC信号通路介导了Orexin-A对AC的作用。食欲素-A的这两种作用同时协同工作，为调节内层视网膜中的信息处理提供了一种特有的方式。
By activating their receptors (OX1R and OX2R) orexin-A/B regulate wake/sleeping states, feeding behaviors, but the function of these peptides in the retina remains unknown. Using patch-clamp recordings and calcium imaging in rat isolated retinal cells, we demonstrated that orexin-A suppressed α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-preferring receptor-mediated currents (AMPA-preferring currents) in ganglion cells (GCs) through OX1R, but potentiated those in amacrine cells (ACs) through OX2R. Consistently, in rat retinal slices orexin-A suppressed light-evoked AMPA-preferring receptor-mediated excitatory postsynaptic currents in GCs, but potentiated those in ACs. Intracellular dialysis of GDP-β-S or preincubation with the Gi/oinhibitor pertussis toxin (PTX) abolished both the effects. Either cAMP/the protein kinase A (PKA) inhibitor Rp-cAMP or cGMP/the PKG blocker KT5823 failed to alter the orexin-A effects. Whilst both of them involved activation of protein kinase C (PKC), the effects on GCs and ACs were respectively eliminated by the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor and phosphatidylcholine (PC)-PLC inhibitor. Moreover, in GCs orexin-A increased [Ca2+]iand the orexin-A effect was blocked by intracellular Ca2+-free solution and by inositol 1,4,5-trisphosphate (IP3) receptor antagonists. In contrast, orexin-A did not change [Ca2+]iin ACs and the orexin-A effect remained in intracellular or extracellular Ca2+-free solution. We conclude that a distinct Gi/o/PI-PLC/IP3/Ca2+-dependent PKC signaling pathway, following the activation of OX1R, is likely responsible for the orexin-A effect on GCs, whereas a Gi/o/PC-PLC/Ca2+-independent PKC signaling pathway, following the activation of OX2R, mediates the orexin-A effect on ACs. These two actions of orexin-A, while working in concert, provide a characteristic way for modulating information processing in the inner retina.
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影响因子：
3.4
作者：
Yoshida, Y;Fujiki, N;Nishino, S
通讯作者：
Nishino, S
影响因子：
9.3
作者：
Jam-Inn Tzeng;Bing-Chang Chen;Huey-Mei Chang;Jhi-Joung Wang;M. Sureshbabu;M. Chien;M. Hsu;M. Bien;W. Chiu;C. Hong;Chien-Huang Lin
通讯作者：
Jam-Inn Tzeng;Bing-Chang Chen;Huey-Mei Chang;Jhi-Joung Wang;M. Sureshbabu;M. Chien;M. Hsu;M. Bien;W. Chiu;C. Hong;Chien-Huang Lin
影响因子：
16.2
作者：
Li, Y;Gao, XB;van den Pol, AN
通讯作者：
van den Pol, AN
DOI：
10.1523/jneurosci.3653-05.2006
发表时间：
2006-01
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Yong-Chun Yu;L. Cao;Xiong-Li Yang
通讯作者：
Yong-Chun Yu;L. Cao;Xiong-Li Yang
影响因子：
9.2
作者：
Leon Lagnado
通讯作者：
Leon Lagnado