title: Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures.
abstract: 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 model 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.
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Naiyong
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Faying
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi 276003, Shandong Province, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Che
authors.affiliation: Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong Province, China.
authors.forename: Guozhao
authors.initials: G
authors.lastname: Ma
keywords: ATP-sensitive potassium channel; activator of mitochondrial ATP-sensitive potassium channel; cytotoxicity; diazoxide; epilepsy; grants-supported paper; hippocampal neuron; inwardly rectifying potassium channel subunit; neural regeneration; neuroprotection; neuroregeneration