Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria

Abstract

Brain mitochondrial ATP‐sensitive K+ channel (mitoKATP) opening by diazoxide protects against ischemic damage and excitotoxic cell death. Here we studied the redox properties of brain mitoKATP . MitoKATP activation during excitotoxicity in cultured cerebellar granule neurons prevented the accumulation of reactive oxygen species (ROS) and cell death. Furthermore, mitoKATP activation in isolated brain mitochondria significantly prevented H2O2 release by these organelles but did not change Ca2+ accumulation capacity. Interestingly, the activity of mitoKATP was highly dependent on redox state. The thiol reductant mercaptopropionylglycine prevented mitoKATP activity, whereas exogenous ROS activated the channel. In addition, the use of mitochondrial substrates that led to higher levels of endogenous mitochondrial ROS release closely correlated with enhanced K+ transport activity through mitoKATP . Altogether, our results indicate that brain mitoKATP is a redox‐sensitive channel that controls mitochondrial ROS release