Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6270816 | Neuroscience | 2016 | 8 Pages |
Abstract
Sigma receptor (ÏR), a unique receptor family, is classified into three subtypes: ÏR1, ÏR2 and ÏR3. It was previously shown that ÏR1 activation induced by 1 μM 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 Ca2+-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 (50 μM) 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 ÏR1 antagonist BD1047, suggesting the involvement of ÏR1. The SKF (50 μM) 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 (50 μM) 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 (50 μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50 μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50 μM) effect is Ca2+-independent, PKG-dependent, but not involving PKA, PI-PLC pathways.
Keywords
MK-801KT5720PPRNMDARPKCPKGU73122SKFPLCPI-PLCKT5823TTXpKaAMPAREGTAHEPESGö69764-(2-hydroxyethyl)-1-piperazineethanesulfonic acidBiPDMSOPhosphatidylinositol-specific phospholipase C[Ca2+]iethylene glycol tetraacetic acidNeurotransmissiontetrodotoxinexcitatory postsynaptic currentdizocilpineDimethyl sulfoxideganglion cellRetinaintracellular calcium concentrationphospholipase Cpaired-pulse ratioBinding immunoglobulin Proteinprotein kinase Aprotein kinase GProtein kinase CAMPA receptorN-methyl-d-aspartate receptorSigma receptor
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Authors
Lei-Lei Liu, Qin-Qin Deng, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong,