title: K+ channel modulation causes genioglossus inhibition in REM sleep and is a strategy for reactivation.
abstract: Rapid eye movement (REM) sleep is accompanied by periods of upper airway motor suppression that cause hypoventilation and obstructive apneas in susceptible individuals. A common idea has been that upper airway motor suppression in REM sleep is caused by the neurotransmitters glycine and γ-amino butyric acid (GABA) acting at pharyngeal motor pools to inhibit motoneuron activity. Data refute this as a workable explanation because blockade of this putative glycine/GABAergic mechanism releases pharyngeal motor activity in all states, and least of all in REM sleep. Here we summarize a novel motor-inhibitory mechanism that suppresses hypoglossal motor activity largely in REM sleep, this being a muscarinic receptor mechanism linked to G-protein-coupled inwardly rectifying potassium (GIRK) channels. We then outline how this discovery informs efforts to pursue therapeutic targets to reactivate hypoglossal motor activity throughout sleep via potassium channel modulation. One such target is the inwardly rectifying potassium channel Kir2.4 whose expression in the brain is almost exclusive to cranial motor nuclei.
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Grace
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Hughes
authors.forename: Shahram
authors.initials: S
authors.lastname: Shahabi
authors.forename: Richard L
authors.initials: RL
authors.lastname: Horner
mesh_terms: D000818:Animals; D006801:Humans; D007002:Hypoglossal Nerve / Q000502:physiology; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology*; D012891:Sleep Apnea Syndromes / Q000188:drug therapy / Q000503:physiopathology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D011976:Receptors, Muscarinic
keywords: Genioglossus muscle; Hypoglossal motor nucleus; Medulla; Obstructive sleep apnea; Sleep