title: Orexin-A differentially modulates AMPA-preferring responses of ganglion cells and amacrine cells in rat retina.
abstract: 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/o inhibitor 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 [Ca(2+)]i and the orexin-A effect was blocked by intracellular Ca(2+)-free solution and by inositol 1,4,5-trisphosphate (IP3) receptor antagonists. In contrast, orexin-A did not change [Ca(2+)]i in ACs and the orexin-A effect remained in intracellular or extracellular Ca(2+)-free solution. We conclude that a distinct Gi/o/PI-PLC/IP3/Ca(2+)-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/Ca(2+)-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.
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China; Cell Electrophysiology Laboratory, Wannan Medical College, 22 West Wenchang Road, Wuhu, Anhui 241002, China.
authors: Chao
authors: C
authors: Zheng
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Qin-Qin
authors: QQ
authors: Deng
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Lei-Lei
authors: LL
authors: Liu
authors: Cell Electrophysiology Laboratory, Wannan Medical College, 22 West Wenchang Road, Wuhu, Anhui 241002, China.
authors: Meng-Ya
authors: MY
authors: Wang
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Gong
authors: G
authors: Zhang
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Wen-Long
authors: WL
authors: Sheng
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Shi-Jun
authors: SJ
authors: Weng
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: xlyang@fudan.edu.cn.
authors: Xiong-Li
authors: XL
authors: Yang
authors: Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: ymzhong@fudan.edu.cn.
authors: Yong-Mei
authors: YM
authors: Zhong
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D000068797:Orexins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D000068796:Orexin Receptor Antagonists; D000068797:Orexins; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D012433:Ryanodine; D018698:Glutamic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium
keywords: AMPA-preferring receptor; Amacrine cells; Ganglion cells; Neuromodulation; Orexin-A; Retina