The regulation of rotenone-induced inflammatory factor production by ATP-sensitive potassium channel expressed in BV-2 cells

Abstract

Our previous studies have demonstrated that activating ATP-sensitive potassium channel (K ATP channel), not only improved Parkinsonian behavior and neurochemical symptoms, but also reduced iNOS activity and mRNA levels in striatum and nigra of rotenone rat model of Parkinson's disease (PD). In this study, it was first shown that the subunits of K ATP channels are expressed in BV-2 cells, and then it was investigated whether K ATP channel was involved in regulating inflammatory factor production from BV-2 cells activated by rotenone. It was found that K ATP channel was expressed in BV-2 cell and formed by the combination of Kir 6.1 and SUR 2A/2B. K ATP channel openers (KCOs) including pinacidil, diazoxide and iptakalim (Ipt) exerted beneficial effects on rotenone-induced morphological alterations of BV-2 cells, decreased tumor necrosis factor alpha (TNF-alpha) production and the expression and activity of inducible isoform of nitric oxide synthase (iNOS). Either glibenclamide or 5-hydroxydecanoate acid (a selective mitochondrial K ATP channel blocker) could abolish the effects of KCOs, suggesting that K ATP channels, especially mitochondrial ATP-sensitive potassium channels (mitoK ATP channels), played a crucial role in preventing the activation of BV-2 cells, and subsequently the production of a variety of proinflammatory factors. Therefore, activation of K ATP channel might be a new therapeutic strategy for treating neuroinflammatory and neurodegenerative disorders.