Summary
Metabolism plays an important role in the maintenance of vigilance states (e.g. wake, NREM, and REM). Brain lactate fluctuations are a biomarker of sleep. Increased interstitial fluid (ISF) lactate levels are necessary for arousal and wake-associated behaviors, while decreased ISF lactate is required for sleep. ATP-sensitive potassium (K ATP ) channels couple glucose-lactate metabolism with neuronal excitability. Therefore, we explored how deletion of neuronal K ATP channel activity (Kir6.2-/- mice) affected the relationship between glycolytic flux, neuronal activity, and sleep/wake homeostasis. Kir6.2-/- mice shunt glucose towards glycolysis, reduce neurotransmitter synthesis, dampen cortical EEG activity, and decrease arousal. 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 each vigilance state and providing the metabolic flexibility to transition between states.
Highlights
Glycolytic flux is necessary for neurotransmitter synthesis. In its absence, neuronal activity is compromised causing changes in arousal and vigilance states despite sufficient energy availability.
With Kir6.2-K ATP channel deficiency, the ability to both maintain and shift between different vigilance states is compromised due to changes in glucose utilization.
Kir6.2-K ATP channels are metabolic sensors under circadian control that gate arousal and sleep/wake transitions.
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