Enhanced MK-801-induced locomotion in Kir6.2 knockout mice

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.

► Kir6.2 knockout increases MK-801-locomotor activity. ► Kir6.2 deficiency enhances neuronal activity. ► Kir6.2-containing K-ATP channel is involved in schizophrenia.