Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep

Study Questions:

Can manipulation of muscarinic muscle receptors reverse pharyngeal muscle suppression found in rapid eye movement (REM) sleep, which leads to hypoventilation in sleep apnea?

Methods:

Experiments were performed on 34 rats, chronically implanted with electrodes recording electroencephalograms (EEGs) and electromyograms (EMGs) of the genioglossus muscle. Microdialysis probes were surgically placed at the hypoglossal motor nucleus and perfused with control solutions or muscarinic receptor agonist, and then a G-protein-coupled inwardly rectifying potassium (GIRK) channel blocker. Sleep stages were scored from analysis of EEG and EMG recordings.

Results:

The study showed 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. The authors also showed that muscarinic inhibition of the genioglossus muscle is functionally linked to GIRK channel activation.

Conclusions:

The authors identified a new cholinergic-GIRK channel mechanism operating at the hypoglossal motor pool in rats 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.

Perspective:

Tongue muscle activity is suppressed during periods of REM sleep, and causes obstructive sleep apnea in humans. The authors identified a new mechanism mediating inhibition of pharyngeal muscles in REM sleep. This new knowledge may lead to new and rational pharmacologic strategies aimed at preventing REM sleep suppression of the pharyngeal musculature associated with obstructive apneic events.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Sleep Apnea

Keywords: Pharyngeal Muscles, Electrodes, GTP-Binding Proteins, Wakefulness, Sleep Apnea Syndromes, Electroencephalography, Potassium, Hypoventilation, Pharynx, Electromyography, Microdialysis, Muscarinic Agonists


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