RATIONALE: Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause of hypoventilation and obstructive sleep apnea in humans. One explanation posits that the neurotransmitters glycine and γ-aminobutyric acid are responsible for REM sleep motor inhibition. However, blockade of that mechanism at cranial motor nuclei increases motor activity in all sleep-wake states, and least of all in REM sleep, arguing against it as a major mechanism of REM sleep pharyngeal motor inhibition. OBJECTIVES: To identify the mechanism of REM sleep inhibition at the hypoglossal motor pool. METHODS: Genioglossus and diaphragm activities were recorded in 34 rats across sleep-wake states. Microdialysis probes were implanted into the hypoglossal motor pool. MEASUREMENTS AND MAIN RESULTS: Here we show that muscarinic receptor antagonism at the hypoglossal motor pool prevents the inhibition of genioglossus activity throughout REM sleep; likewise, with G-protein-coupled inwardly rectifying potassium (GIRK) channel blockade. Importantly, the genioglossus activating effects of these interventions were largest in REM sleep and minimal or often absent in other sleep-wake states. Finally, we showed that muscarinic inhibition of the genioglossus is functionally linked to GIRK channel activation. CONCLUSIONS: We identify a powerful cholinergic-GIRK channel mechanism operating at the hypoglossal motor pool that has its largest inhibitory influence in REM sleep and minimal or no effects in other sleep-wake states. This mechanism is the major cause of REM sleep inhibition at a pharyngeal motor pool critical for effective breathing.
RATIONALE: Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause of hypoventilation and obstructive sleep apnea in humans. One explanation posits that the neurotransmitters glycine and γ-aminobutyric acid are responsible for REM sleep motor inhibition. However, blockade of that mechanism at cranial motor nuclei increases motor activity in all sleep-wake states, and least of all in REM sleep, arguing against it as a major mechanism of REM sleep pharyngeal motor inhibition. OBJECTIVES: To identify the mechanism of REM sleep inhibition at the hypoglossal motor pool. METHODS: Genioglossus and diaphragm activities were recorded in 34 rats across sleep-wake states. Microdialysis probes were implanted into the hypoglossal motor pool. MEASUREMENTS AND MAIN RESULTS: Here we show that muscarinic receptor antagonism at the hypoglossal motor pool prevents the inhibition of genioglossus activity throughout REM sleep; likewise, with G-protein-coupled inwardly rectifying potassium (GIRK) channel blockade. Importantly, the genioglossus activating effects of these interventions were largest in REM sleep and minimal or often absent in other sleep-wake states. Finally, we showed that muscarinic inhibition of the genioglossus is functionally linked to GIRK channel activation. CONCLUSIONS: We identify a powerful cholinergic-GIRK channel mechanism operating at the hypoglossal motor pool that has its largest inhibitory influence in REM sleep and minimal or no effects in other sleep-wake states. This mechanism is the major cause of REM sleep inhibition at a pharyngeal motor pool critical for effective breathing.
Authors: Luigi Taranto-Montemurro; Ludovico Messineo; Scott A Sands; Ali Azarbarzin; Melania Marques; Bradley A Edwards; Danny J Eckert; David P White; Andrew Wellman Journal: Am J Respir Crit Care Med Date: 2019-05-15 Impact factor: 21.405
Authors: David G McSharry; Julian P Saboisky; Pam Deyoung; Amy S Jordan; John Trinder; Erik Smales; Lauren Hess; Nancy L Chamberlin; Atul Malhotra Journal: Sleep Date: 2014-03-01 Impact factor: 5.849
Authors: R Nisha Aurora; Ciprian Crainiceanu; Daniel J Gottlieb; Ji Soo Kim; Naresh M Punjabi Journal: Am J Respir Crit Care Med Date: 2018-03-01 Impact factor: 21.405