Abstract
ATP modulates voltage- and ligand-gated channels in the CNS via the activation of ionotropic P2X and metabotropic P2Y receptors. While P2Y receptors are expressed in retinal neurons, the function of these receptors in the retina is largely unknown. Using whole-cell patch-clamp techniques in rat retinal slice preparations, we demonstrated that ATP suppressed glycine receptor-mediated currents of OFF type ganglion cells (OFF-GCs) dose-dependently, and the effect was in part mediated by P2Y1 and P2Y11, but not by P2X. The ATP effect was abolished by intracellular dialysis of a Gq/11 protein inhibitor and phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor, but not phosphatidylcholine (PC)-PLC inhibitor. The ATP effect was accompanied by an increase in [Ca2+]i through the IP3-sensitive pathway and was blocked by intracellular Ca2+-free solution. Furthermore, the ATP effect was eliminated in the presence of PKC inhibitors. Neither PKA nor PKG system was involved. These results suggest that the ATP-induced suppression may be mediated by a distinct Gq/11/PI-PLC/IP3/Ca2+/PKC signaling pathway, following the activation of P2Y1,11 and other P2Y subtypes. Consistently, ATP suppressed glycine receptor-mediated light-evoked inhibitory postsynaptic currents of OFF-GCs. These results suggest that ATP may modify the ON-to-OFF crossover inhibition, thus changing action potential patterns of OFF-GCs.
Highlights
ATP modulates voltage- and ligand-gated channels in the CNS via the activation of ionotropic P2X and metabotropic P2Y receptors
Using whole-cell patch-clamp techniques in rat retinal slice preparations, we demonstrated that ATP suppressed glycine receptor-mediated currents of OFF type ganglion cells (OFF-Ganglion cells (GCs)) dose-dependently, and the effect was in part mediated by P2Y1 and P2Y11, but not by P2X
In the retina it has been previously reported that ATP released from Müller cells and retinal neurons modulates the activity of GCs
Summary
ATP modulates voltage- and ligand-gated channels in the CNS via the activation of ionotropic P2X and metabotropic P2Y receptors. Neither PKA nor PKG system was involved These results suggest that the ATP-induced suppression may be mediated by a distinct Gq/11/PI-PLC/IP3/Ca2+/PKC signaling pathway, following the activation of P2Y1,11 and other P2Y subtypes. As a neurotransmitter in the CNS, ATP functions by acting on two distinct subfamilies of P2 purinoceptors: seven ionotropic P2X receptors (P2X1-7) and eight metabotropic mammalian P2Y receptors (P2Y1,2,4,6,11,12,13,14)[1,2] These receptors are involved in regulating voltage-gated Ca2+, K+ channels, ligand-gated NMDA channels[3,4,5,6,7,8,9,10] and neurotransmitter release[11,12,13]. Because of the importance of OFF-GCs in the ON-to-OFF crossover inhibition and the essential role of glycinergic signal in shaping temporal features of OFF-GC responses, the present work focused on ATP-induced www.nature.com/scientificreports/
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