@article {Ji12744, author = {Min Ji and Yanying Miao and Ling-Dan Dong and Jie Chen and Xiao-Fen Mo and Shi-Xiang Jiang and Xing-Huai Sun and Xiong-Li Yang and Zhongfeng Wang}, title = {Group I mGluR-Mediated Inhibition of Kir Channels Contributes to Retinal M{\"u}ller Cell Gliosis in a Rat Chronic Ocular Hypertension Model}, volume = {32}, number = {37}, pages = {12744--12755}, year = {2012}, doi = {10.1523/JNEUROSCI.1291-12.2012}, publisher = {Society for Neuroscience}, abstract = {M{\"u}ller cell gliosis, which is characterized by upregulated expression of glial fibrillary acidic protein (GFAP), is a universal response in many retinal pathological conditions. Whether down-regulation of inward rectifying K+ (Kir) channels, which commonly accompanies the enhanced GFAP expression, could contribute to M{\"u}ller cell gliosis is poorly understood. We investigated changes of Kir currents, GFAP and Kir4.1 protein expression in M{\"u}ller cells in a rat chronic ocular hypertension (COH) model, and explored the mechanisms underlying M{\"u}ller cell gliosis. We show that Kir currents and Kir4.1 protein expression in M{\"u}ller cells were reduced significantly, while GFAP expression was increased in COH rats, and these changes were eliminated by MPEP, a group I metabotropic glutamate receptors (mGluR I) subtype mGluR5 antagonist. In normal isolated M{\"u}ller cells, the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) suppressed the Kir currents and the suppression was blocked by MPEP. The DHPG effect was mediated by the intracellular Ca2+-dependent PLC/IP3-ryanodine/PKC signaling pathway, but the cAMP-PKA pathway was not involved. Moreover, intravitreal injection of DHPG in normal rats induced changes in M{\"u}ller cells, similar to those observed in COH rats. The DHPG-induced increase of GFAP expression in M{\"u}ller cells was obstructed by Ba2+, suggesting the involvement of Kir channels. We conclude that overactivation of mGluR5 by excessive extracellular glutamate in COH rats could contribute to M{\"u}ller cell gliosis by suppressing Kir channels.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/32/37/12744}, eprint = {https://www.jneurosci.org/content/32/37/12744.full.pdf}, journal = {Journal of Neuroscience} }