ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39964713.
- Also identified by DOI 10.1073/pnas.2416578122 and PMC identifier 11874466.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>ATP</sub>) channels couple glucose-lactate metabolism with excitability. Using mice lacking K<sub>ATP</sub> channel activity (e.g., Kir6.2<sup>-/-</sup> mice), we explored how changes in glucose utilization affect cortical electroencephalography (EEG) activity and sleep/wake homeostasis. In the brain, Kir6.2<sup>-/-</sup> mice shunt glucose toward glycolysis, reducing neurotransmitter biosynthesis and dampening cortical EEG activity. Kir6.2<sup>-/-</sup> 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<sub>ATP</sub> 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.
Medical subject headings
- Sleep
- Glycolysis
- Potassium Channels, Inwardly Rectifying
- KATP Channels
- Cerebral Cortex