The Kir channel in the nucleus tractus solitarius integrates the chemosensory system with REM sleep executive machinery for homeostatic balance

• Published in: Scientific reports 2024-09, Vol.14 (1), p.21651-16, Article 21651
• Main Authors: Mir, Fayaz A., Jha, Sushil K.
• Format: Article
• Language: English
• Subjects: 631/378; 631/378/1385; 631/443; Acidity; Animals; Apnea; Barium; Barium Compounds - pharmacology; Brain stem; Chemoreception; Chlorides - metabolism; Drug delivery; Eye movements; Homeostasis; Humanities and Social Sciences; Hydrogen; Hypercapnia; Ion channels; Locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - metabolism; Locus Coeruleus - physiology; Male; Microinjection; multidisciplinary; NREM sleep; Potassium channels (inwardly-rectifying); Potassium Channels, Inwardly Rectifying - metabolism; Potassium inward rectifier channels; Rats; Rats, Wistar; REM sleep; Retrotrapezoid nucleus; Rett syndrome; Science; Science (multidisciplinary); Sensors; Sleep; Sleep and wakefulness; Sleep disorders; Sleep, REM - physiology; Sodium channels; Solitary Nucleus - metabolism; Solitary Nucleus - physiology; Solitary tract nucleus; Wakefulness - physiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71818-0

The locus coeruleus (LC), nucleus tractus solitarius (NTS), and retrotrapezoid nucleus (RTN) are critical chemosensory regions in the brainstem. In the LC, acid-sensing ion channels and proton pumps serve as H + sensors and facilitate the transition from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. Interestingly, the potassium inward rectifier (KIR) channels in the LC, NTS, and RTN also act as H + -sensors and are a primary target for improving sleep in obstructive sleep apnea and Rett syndrome patients. However, the role of Kir channels in NREM to REM sleep transition for H + homeostasis is not known. Male Wistar rats were surgically prepared for chronic sleep–wake recording and drug delivery into the LC, NTS, and RTN. In different animal cohorts, microinjections of the Kir channel inhibitor, barium chloride (BaCl 2 ), at concentrations of 1 mM (low dose) and 2 mM (high dose) in the LC and RTN significantly increased wakefulness and decreased NREM sleep. However, BaCl 2 microinjection into the LC notably reduced REM sleep, whereas it didn’t change in the RTN-injected group. Interestingly, BaCl 2 microinjections into the NTS significantly decreased wakefulness and increased the percent amount of NREM and REM sleep. Additionally, with the infusion of BaCl 2 into the NTS, the mean REM sleep episode numbers significantly increased, but the length of the REM sleep episode didn’t change. These findings suggest that the Kir channels in the NTS, but not in the LC and RTN, modulate state transition from NREM to REM sleep.