Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures  

作　　者：Qingxi Fu Zhiqing Sun Jinling Zhang Naiyong Gao Faying Qi Fengyuan Che Guozhao Ma 

机构地区：[1]Department of Neurology, Linyi People's Hospital [2]Department of Neurology, Shandong Provincial Hospital, Shandong University

出　　处：《Neural Regeneration Research》2013年第11期1000-1006,共7页中国神经再生研究（英文版）

基　　金：supported by the Technology Development Plan of Linyi City, No. 201113002

摘　　要：Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular mode of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel （Kir） subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits.Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular mode of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel （Kir） subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits.

关 键 词：neural regeneration ATP-sensitive potassium channel activator of mitochondrial ATP-sensitivepotassium channel epilepsy DIAZOXIDE inwardly recti^ing potassium channel subunit hippocampal neuron CYTOTOXICITY neuroprotection grants-supported paper NEUROREGENERATION 

分 类 号：R742.1[医药卫生—神经病学与精神病学]