title: Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells.
abstract: Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. The SKF (50μM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50μM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-β-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways.
authors.affiliation: 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.forename: Lei-Lei
authors.initials: LL
authors.lastname: Liu
authors.affiliation: 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.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Deng
authors.affiliation: 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.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Weng
authors.affiliation: 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.forename: Xiong-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: 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.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D008027:Light; D008297:Male; D018408:Patch-Clamp Techniques; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D002227:Carbazoles; D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D005029:Ethylenediamines; D018091:Receptors, AMPA; D017480:Receptors, sigma; C073601:KT 5823; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D018698:Glutamic Acid; C012134:SK&F 10047; D017869:Cyclic GMP-Dependent Protein Kinases; D010620:Phenazocine; D002118:Calcium
keywords: AMPA receptor; excitatory postsynaptic current; ganglion cell; neurotransmission; retina; σR1