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泛连接蛋白通道对两栖动物视网膜后像信号的作用。

Contribution of pannexin channels to afterimage signals in the amphibian retina.

作者信息

Liu Yufei, Libian Nick, Jiang Zheng, Shen Wen

机构信息

Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, United States.

Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.

出版信息

Am J Physiol Cell Physiol. 2025 Aug 1;329(2):C355-C365. doi: 10.1152/ajpcell.00028.2025. Epub 2025 Jun 23.

Abstract

Pannexin 1 (Panx1) forms large-pore, single-membrane channels that connect the intracellular and extracellular environments, permitting the passage of ions and small molecules, such as ATP. Panx1 channels are involved in diverse signaling pathways that contribute to various physiological processes, including sensory processing, although their precise mechanisms of action remain incompletely understood. This study reveals a Panx1-mediated mechanism regulating visual signal processing in the amphibian retina. Using immunolabeling and confocal imaging, we localized Panx1 channels in the cone-dominated On-bipolar cells, specifically at both somas and axon terminals. Whole cell patch-clamp recordings showed that these channels have high permeability to Cl ions, which can be blocked by Panx1 peptide, carbenoxolone, and mefloquine, all recognized as Panx1 inhibitors. Blocking Panx1 channels or reducing external Cl concentrations significantly increased bright light-induced delayed spontaneous excitatory responses in ganglion cells, indicating an inhibitory role of Panx1 channels at the bipolar cell synaptic release. These delayed spontaneous responses in ganglion cells, known as rebound currents, are associated with afterimage signals in the retina. Our findings suggest that Panx1 channels help prevent overexcitation associated with bright light-induced afterimage phenomena. Cl permeable Panx1 channels in the On-bipolar cells serve as a novel mechanism for the negative control of overexcitation in afterimage signal processing in the retina.

摘要

泛素连接蛋白1(Panx1)形成大孔单膜通道,连接细胞内和细胞外环境,允许离子和小分子(如ATP)通过。Panx1通道参与多种信号通路,这些通路有助于各种生理过程,包括感觉处理,尽管其确切作用机制仍未完全了解。本研究揭示了一种Panx1介导的调节两栖动物视网膜视觉信号处理的机制。通过免疫标记和共聚焦成像,我们将Panx1通道定位在视锥细胞主导的ON双极细胞中,特别是在胞体和轴突末端。全细胞膜片钳记录显示,这些通道对Cl离子具有高渗透性,可被Panx1肽、羧苄青霉素和甲氟喹阻断,这些都被认为是Panx1抑制剂。阻断Panx1通道或降低细胞外Cl浓度显著增加了强光诱导的神经节细胞延迟自发兴奋性反应,表明Panx1通道在双极细胞突触释放中起抑制作用。神经节细胞中的这些延迟自发反应,称为反弹电流,与视网膜中的后像信号有关。我们的研究结果表明,Panx1通道有助于防止与强光诱导的后像现象相关的过度兴奋。ON双极细胞中可通透Cl的Panx1通道是视网膜后像信号处理中过度兴奋负调控的一种新机制。

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