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.