ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep

作者：Nicholas J. Constantino, Caitlin M. Carroll, Holden C. Williams, Hemendra J. Vekaria, Carla M. Yuede, Kai Saito, Patrick W. Sheehan, James A. Snipes, Marcus E. Raichle, Erik S. Musiek, Patrick G. Sullivan, Josh M. Morganti, Lance A. Johnson, Shannon L. Macauley · 发表于：Proceedings of the National Academy of Sciences · 年份：2025 · DOI：10.1073/pnas.2416578122 · 被引用次数：9 · 研究领域：Sleep and Wakefulness Research、Neuroscience and Neuropharmacology Research、Neural dynamics and brain function

Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are associated with wakefulness and decreased ISF lactate is required for sleep. ATP-sensitive potassium (K ATP ) channels couple glucose-lactate metabolism with excitability. Using mice lacking K ATP channel activity (e.g., Kir6.2 −/− mice), we explored how changes in glucose utilization affect cortical electroencephalography (EEG) activity and sleep/wake homeostasis. In the brain, Kir6.2 −/− mice shunt glucose toward glycolysis, reducing neurotransmitter biosynthesis and dampening cortical EEG activity. Kir6.2 −/− mice spent more time awake at the onset of the light period due to altered ISF lactate dynamics. Together, we show that Kir6.2-K ATP channels act as metabolic sensors to gate arousal by maintaining the metabolic stability of sleep/wake states and providing the metabolic flexibility to transition between states.