Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Müller cells.

Abstract

Müller cell gliosis is a general response in a variety of pathological alternations of the retina, which is characterized by the upregulated expression of glial fibrillary acidic protein (GFAP) and the downregulation of membrane K(+) conductance. We have demonstrated that downregulation of Kir K(+) currents in Müller cells in an experimental glaucoma model is due to activation of group I metabotropic glutamate receptor (mGluR I) by glutamate, which contributes to Müller cell gliosis. Here, whether and how activation of mGluR I modulate membrane Kir4.1 protein internalization and Kir4.1 mRNA expression were investigated in purified cultured rat retinal Müller cells using immunocytochemistry, Western blot and real-time PCR techniques. DHPG (10μM, a selective mGluR I agonist) treatment induced Müller cell gliosis, as evidenced by enhanced GFAP expression. Although total Kir4.1 proteins extracted from the DHPG-treated cells kept unchanged, Kir4.1 proteins in the cell membrane compartment were significantly decreased, which was prior to the change of GFAP in time course. In addition, DHPG (10 and 100μM) treatment induced a transient decrease in Kir4.1 mRNA expression in the cells. All these results suggest that activation of mGluR I by DHPG may decrease the number of functional Kir4.1 channels in purified cultured rat retinal Müller cells through modulating Kir4.1 protein and mRNA, thus contributing to Müller cell gliosis.

• Authors: Feng Gao, Fang Li, Yanying Miao, Ling-Dan Dong, Sheng-Hai Zhang, Jihong Wu, Xing-Huai Sun, Zhongfeng Wang
• Journal: Neuroscience letters (Neurosci Lett) Vol. 588 Pg. 12-7 (Feb 19 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 25549543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Glial Fibrillary Acidic Protein
• Kcnj10 (channel)
• Potassium Channels, Inwardly Rectifying
• RNA, Messenger
• Receptors, Metabotropic Glutamate
• Resorcinols
• 3,5-dihydroxyphenylglycine
• Glycine

Topics

• Animals
• Animals, Newborn
• Cell Membrane (metabolism)
• Cells, Cultured
• Ependymoglial Cells (drug effects, metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis
• Glycine (analogs & derivatives, pharmacology)
• Potassium Channels, Inwardly Rectifying (genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• Receptors, Metabotropic Glutamate (agonists)
• Resorcinols (pharmacology)