title: Enhanced MK-801-induced locomotion in Kir6.2 knockout mice.
abstract: ATP-sensitive K(+) (K-ATP) channels provide a unique link between cellular energetics and electrical excitability, and also act as a unifying molecular coordinator of the body's response to stress. Although the body's response to stress is implicated in the worsening or relapse of psychotic symptoms in schizophrenia, the role of K-ATP channels remains unclear. Therefore, the aim of the current study was to investigated the effect of K-ATP channels on schizophrenia-like symptoms induced by MK-801 using Kir6.2 (one pore-forming subunit of K-ATP) knockout mice. We demonstrated that Kir6.2 knockout enhanced locomotor activity significantly compared to the wild-type mice after MK-801 administration. Moreover, we found that depletion of Kir6.2 significantly increased the numbers of Arc-positive cells in cortex, hippocampus and striatum in basal state. MK-801 augmented the Arc expression in wild-type mice. Collectively, our findings in this study indicate that K-ATP channels are involved in the regulation of MK-801-induced acute symptoms of schizophrenia, which is associated with the neural excitability. In addition, our results may provide valuable information for the development of new treatments for schizophrenia.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Meng-Di
authors.initials: MD
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Ren-Hong
authors.initials: RH
authors.lastname: Du
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D000099161:Kcnj11 Channel
chemical_list: D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel