Psychiatry Investig.  2008 Jun;5(2):94-101. 10.4306/pi.2008.5.2.94.

Interaction between Neuronal Depolarization and MK-801 in SH-SY5Y Cells and the Rat Cortex

• Kim Y
• Seo M
• Lee YI
• Kim SY
• Cho EA
• Kim SH
• Ahn YM
• Kang UG
• Kim YS
• Juhnn YS

• KMID: 1706122
• DOI: http://doi.org/10.4306/pi.2008.5.2.94

Abstract

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 microM MK-801 for 15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was reintroduced after the KCl 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 3beta (GSK3beta) (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 GSK3beta (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCl in the dephosphorylation of ERK1/2.
CONCLUSION
These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCl or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.

Keyword

AKT; Glycogen synthase kinase 3beta; Extracellular legulated kinase 1/2; KCl; Electro convulsive shock; MK-801

MeSH Terms

Animals
Dizocilpine Maleate*
Electroconvulsive Therapy
Electroshock
Glycogen Synthase Kinases
Humans
Male
Neurons*
Phosphorylation
Phosphotransferases
Psychotic Disorders
Rats*
Rats, Sprague-Dawley
Dizocilpine Maleate
Glycogen Synthase Kinases
Phosphotransferases