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Wen Shen, Yufei Liu, Richard L Chappell, Harris Ripps; A Pannexin-Mediated Purinergic Pathway in the Vertebrate Retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4166.
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Previously, we demonstrated that pannexin 1 channels, known to be ATP release sites in many tissues, are expressed predominately on cone-dominant ON-bipolar cells. The purpose of this study was to demonstrate the importance of the pannexin-mediated purinergic pathway that transmits signals from cone-dominant bipolar cells to rod-dominant bipolar cells in the inner retina.
Whole cell patch-clamp recordings were obtained from bipolar, amacrine and ganglion cells in tiger salamander retinal slices. These cells were used to determine the effects of P2X3 receptors and the selective antagonist A317491 on spontaneous EPSCs, light-evoked EPSCs and voltage-gated Ca2+ channels in response to ATP and its analogs. ATP release from pannexin 1 channels was detected in luciferase-luciferin ATP assay, which could be blocked by application of a specific inhibitor of pannexin 1 channels, 10Panx-1.
We find that increasing extracellular ATP levels - by applying 200microM ATP - suppresses dim light-evoked EPSCs in ganglion cells. Moreover, it inhibits spontaneous release of glutamate from bipolar cells in the dark. Both effects were reversed by A317491, a P2X3 receptor antagonist. However, ATP had a limited effect on cone-dominated light responses in ganglion cells, suggesting that the rod pathway is selectively affected by local ATP levels in the inner plexiform layer. Moreover, exogenous ATP tends to increase IPSCs in ganglion cells, indicating that ATP may increase GABA or glycine release from amacrine cells that initiate IPSCs in ganglion cells. Further evidence shows that ATP and its analogs enhance voltage-gated Ca2+ channels in a group of amacrine cells.
Our results indicate that ATP release via pannexin 1 channels in cone-dominated ON-bipolar cells directly activates P2X3 receptors in amacrine cells. This provides a negative feedback signal to rod-dominated bipolar cells, and results in the suppression of EPSCs in ganglion cells. In addition, this study reveals that the purinergic system by which the inner retina conveys signals from the cone-pathway to the rod pathway is inhibited in the light-adapted retina.
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