Signaling mechanism for modulation by ATP of glycine receptors on rat retinal ganglion cells.
Signaling mechanism for modulation by ATP of glycine receptors on rat retinal ganglion cells.
复制标题
大鼠视网膜神经节细胞甘氨酸受体 ATP 调节的信号机制
DOI：
10.1038/srep28938
复制
发表时间：
2016-06-30
影响因子：
4.6
通讯作者：
Zhong YM
中科院分区：
文献类型：
--
作者：
Zhang PP;Zhang G;Zhou W;Weng SJ;Yang XL;Zhong YM
ATP通过激活亲离子型P2 X和亲代谢型P2 Y受体调节CNS中的电压门控和配体门控通道。虽然P2 Y受体在视网膜神经元中表达，但这些受体在视网膜中的功能在很大程度上是未知的。采用全细胞膜片钳技术，研究了ATP对OFF型神经节细胞（OFF-GCs）甘氨酸受体介导的电流的抑制作用，结果表明ATP对OFF型神经节细胞甘氨酸受体介导的电流的抑制作用呈剂量依赖性，其抑制作用部分由P2 Y1和P2 Y11介导，而不是由P2 X介导。Gq/11蛋白抑制剂和磷脂酰肌醇（PI）-磷脂酶C（PLC）抑制剂的细胞内透析可消除ATP效应，但磷脂酰胆碱（PC）-PLC抑制剂则不能。ATP的作用伴随着[Ca 2 +]i的增加，通过IP 3-敏感的途径，并被细胞内无钙溶液阻断。此外，在PKC抑制剂的存在下，ATP效应被消除。PKA和PKG系统均未参与。这些结果表明，ATP诱导的抑制可能是通过不同的Gq/11/PI-PLC/IP 3/Ca 2 +/PKC信号通路介导的，在P2 Y 1，11和其他P2 Y亚型激活之后。ATP抑制甘氨酸受体介导的光诱发的抑制性突触后电流。这些结果表明，ATP可能会修改ON到OFF的交叉抑制，从而改变动作电位模式的关-GC。
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.