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ATP敏感性钾离子通道开放剂促进大鼠原代培养星形胶质细胞谷氨酸转运体对谷氨酸的摄取
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KATP channel openers facilitate glutamate uptake by GluTs in rat primary cultured astrocytes
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Sun X.-L., Zeng X.-N., Zhou F., Dai C.-P., Ding J.-H., Hu G.
2009/5/29 18:40:20
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Neuropsychopharmacology,
2008,
Volume 33,
Issue 6
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Increasing evidence, including from our laboratory, has revealed that opening of ATP sensitive potassium channels (KATP channels) plays the neuronal protective roles both in vivo and in vitro. Thus KATP channel openers (KCOs) have been proposed as potential neuroprotectants. Our previous studies demonstrated that KATP channels could regulate glutamate uptake activity in PC12 cells as well as in synaptosomes of rats. Since glutamate transporters (GluTs) of astrocytes play crucial roles in glutamate uptake and KATP channels are also expressed in astrocytes, the present study showed whether and how KATP channels regulated the function of GluTs in primary cultured astrocytes. The results showed that nonselective KCO pinacidil, selective mitochondrial KCO diazoxide, novel, and blood-brain barrier permeable KCO iptakalim could enhance glutamate uptake, except for the sarcolemmal KCO P1075. Moreover pinacidil, diazoxide, and iptakalim reversed the inhibition of glutamate uptake induced by 1-methyl-4-phenylpyridinium (MPP+). These potentiated effects were completely abolished by mitochondrial KATP blocker 5-hydroxydecanoate. Furthermore, either diazoxide or iptakalim could inhibit MPP+-induced elevation of reactive oxygen species (ROS) and phosphorylation of protein kinases C (PKC). These findings are the first to demonstrate that activation of KATP channel, especially mitochondrial KATP channel, improves the function of GluTs in astrocytes due to reducing ROS production and downregulating PKC phosphorylation. Therefore, the present study not only reveals a novel pharmacological profile of KCOs as regulators of GluTs, but also provides a new strategy for neuroprotection. © 2008 Nature Publishing Group All rights reserved.
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Correspondence Address:
Hu, G.; Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China; email: ghu@njmu.edu.cn
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疾病资源中心
曹晶珠 邹大进
解放军第二军医大学附属长海医院内分泌科
患者为中年女性，35岁，因“多饮、多尿、全身乏力、闭经1年，体重增加、肝区不适半年”于2008年8月入院。患者2007年感冒后出现多饮、多尿，每日饮水约10,000 ml，未予重视及诊治。2007年出现闭经，在外院妇产科就诊，先后予2次黄体酮肌肉注射，仍未来月经。半年前体重增加25 kg，肝区不适，肝功能示转氨酶升高。患者无便秘腹胀、无皮肤感染、无双下肢水肿，活动后稍感胸闷、气喘，夜尿增多，平均每小时1次。最大体重88.7 kg。既往史无特殊。月经史：初潮14岁，4/28～30，2008年6月。
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