Identification of the mechanism mediating genioglossus muscle suppression in REM sleep.

Abstract:

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

Grace KP,Hughes SW,Horner RL

doi

10.1164/rccm.201209-1654OC

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

311-9

issue

3

eissn

1073-449X

issn

1535-4970

pii

rccm.201209-1654OC

journal_volume

187

pub_type

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