KATP channel openers protect mesencephalic neurons against MPP+-induced cytotoxicity via inhibition of ROS production
✍ Scribed by Juan Xie; Lei Duan; Xia Qian; Xu Huang; Jianhua Ding; Gang Hu
- Book ID
- 102908181
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 893 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Opening of ATP‐sensitive potassium (K~ATP~) channels has been demonstrated to exert significant neuroprotection in in vivo and in vitro models of Parkinson's disease (PD), but the exact mechanism remains unclear. In the present study, various K~ATP~ channel openers (KCOs) sensitive to diverse K~ATP~ subunits were used to clarify the protective role of K~ATP~ channel opening in 1‐methyl‐4‐phenylpyridinium (MPP^+^)‐induced oxidative stress injury in mouse primary cultured mesencephalic neurons. The results showed that pretreatment with nonselective KCO pinacidil (Pin) or diazoxide (Dia), a KCO sensitive to Kir6.2/SUR1 K~ATP~ channels, protected mesencephalic neurons, especially dopaminergic neurons, against MPP^+^‐induced injury in a concentration‐dependent manner. However, cromakalim (Cro), an opener of Kir6.1/SUR2 but not Kir6.2/SUR1 K~ATP~ channels, failed to protect against MPP^+^‐induced cytotoxicity. Furthermore, Pin and Dia but not Cro significantly suppressed the elevation of reactive oxygen species (ROS) triggered by MPP^+^ and prevented the loss of mitochondrial member potential (ΔΨm) and the release of mitochondrial cyotchrome c. Consequently, opening of K~ATP~ channels expressed in neurons could protect primary mesencephalic neurons against MPP^+^‐induced cytotoxicity via inhibiting ROS overproduction and subsequently ameliorating mitochondrial function. © 2009 Wiley‐Liss, Inc.