title: beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure.
abstract: Nicotine exposure diminishes the protective breathing and arousal responses to stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance could underpin the well established association between smoking and the increased risk of sudden infant death syndrome. We show here that the protective responses to stress during sleep are partially regulated by particular nicotinic acetylcholine receptors (nAChRs). We compared responses of sleeping wild-type and mutant mice lacking the beta2 subunit of the nAChR to episodic hypoxia. Arousal from sleep was diminished, and breathing drives accentuated in mutant mice indicating that these protective responses are partially regulated by beta2-containing nAChRs. Brief exposure to nicotine significantly reduced breathing drives in sleeping wild-type mice, but had no effect in mutants. We propose that nicotine impairs breathing (and possibly arousal) responses to stress by disrupting functions normally regulated by beta2-containing, high-affinity nAChRs.
authors.affiliation: Laboratoire de Neurologie et de Physiologie du Développement, Institut National de la Santé et de la Recherche Médicale E9935, Hôpital Robert-Debré, 75019 Paris, France.
authors.forename: Gary
authors.initials: G
authors.lastname: Cohen
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Han
authors.forename: Régis
authors.initials: R
authors.lastname: Grailhe
authors.forename: Jorge
authors.initials: J
authors.lastname: Gallego
authors.forename: Claude
authors.initials: C
authors.lastname: Gaultier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Changeux
authors.forename: Hugo
authors.initials: H
authors.lastname: Lagercrantz
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000378:metabolism; D000860:Hypoxia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep; D012893:Sleep Wake Disorders / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D013312:Stress, Physiological; D013997:Time Factors
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine