ACTIVATION OF THE SIGMA RECEPTOR 1 MODULATES AMPA RECEPTOR-MEDIATED LIGHT-EVOKED EXCITATORY POSTSYNAPTIC CURRENTS IN RAT RETINAL GANGLION CELLS

Sigma receptor (sigma R), a unique receptor family, is classified into three subtypes: sigma R1, sigma R2 and sigma R3. It was previously shown that sigma R1 activation induced by 1 mu M 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 mu M) 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 sigma R1 antagonist BD1047, suggesting the involvement of sigma R1. The SKF (50 mu M) 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 mu M) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-beta-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50 mu M) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50 mu M) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50 mu M) effect is Ca2+-independent, PKG-dependent, but not involving PKA, PI -PLC pathways. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.