Interaction between neuronal depolarization and MK-801 in SH-SY5Y cells and the rat cortex

Objective The interaction between MK-801, a model of psychosis and KCl-induced depolarization or electroconvulsive shock (ECS), a therapeutic model of electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat frontal cortex. Methods SH-SY5Y cells were pretreated with 1 μM MK-801 for 15 min, followed by cotreatment with 100 mM KC1 for 5 min. MK-801 was reintroduced after the KC1 was washed out, and the samples were incubated before harvesting. For the experiments in rats, male Sprague-Dawley rats were treated with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase 3 β (GSK3β) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK) 1/2 in SH-SY5Y cells and the rat frontal cortex were performed. Results KCl-induced neuronal depolarization resulted in the transient dephosphorylation of AKT (Ser473) and GSK3β (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KC1 inhibited the initial dephosphorylation of AKT and GSK3β produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3β (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3β (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCI in the dephosphorylation of ERK1/2. Conclusion These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCI or ECS is involved the regulation of AKT (Ser473) and GSK3 β (Ser9) phosphorylation.