Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.

Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.
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腺苷及腺苷受体拮抗剂对慢性高眼压模型大鼠Muller细胞钾通道的影响

DOI:
10.1038/srep11294
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发表时间:
2015-06-11
期刊:
影响因子:
4.6
通讯作者:
Zhong Y
Zhong Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yang Z;Huang P;Liu X;Huang S;Deng L;Jin Z;Xu S;Shen X;Luo X;Zhong Y

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Müller细胞是大鼠视网膜中主要的胶质细胞,在青光眼研究中受到广泛关注。然而,目前尚不清楚腺苷和腺苷受体(AR)拮抗剂是否在Müller细胞钾通道的调节中发挥任何作用,并随后促进谷氨酰胺合成酶(GS)和L-谷氨酸/L-天冬氨酸转运蛋白(GLAST)功能。结果发现,慢性高眼压(COH)可下调Müller细胞Kir2.1、Kir4.1、ASK-1、GS和GLAST的表达,减弱内向钾电流峰值。COH组大鼠视网膜神经节细胞(RGC)计数低于假手术组。玻璃体内注射选择性A2 A受体拮抗剂SCH 442416可上调Müller细胞Kir4.1、ASK-1、GS和GLAST的表达,增强内向钾电流。同时,在COH大鼠中玻璃体内注射SCH 442416后的RGC计数高于溶剂注射后。PKA抑制剂H-89阻断这些SCH 442416作用的事实表明PKA信号传导途径参与玻璃体内注射SCH 442416后观察到的眼部反应。
Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection.
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