beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure.
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.
Cohen
Gary
G
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.
Han
Zhi-Yan
ZY
Grailhe
Régis
R
Gallego
Jorge
J
Gaultier
Claude
C
Changeux
Jean-Pierre
JP
Lagercrantz
Hugo
H
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
D011978:Receptors, Nicotinic; D009538:Nicotine