title: Ventilatory pattern and chemosensitivity in M1 and M3 muscarinic receptor knockout mice.
abstract: Acetylcholine (ACh) acting through muscarinic receptors is thought to be involved in the control of breathing, notably in central and peripheral chemosensory afferents and in regulations related to sleep-wake states. By using whole-body plethysmography, we compared baseline breathing at rest and ventilatory responses to acute exposure (5 min) to moderate hypoxia (10% O(2)) and hypercapnia (3 and 5% CO(2)) in mice lacking either the M(1) or the M(3) muscarinic receptor, and in wild-type matched controls. M(1) knockout mice showed normal minute ventilation (V(E)) but elevated tidal volume (V(T)) at rest, and normal chemosensory ventilatory responses to hypoxia and hypercapnia. M(3) knockout mice had elevated V(E) and V(T) at rest, a reduced V(T) response slope to hypercapnia, and blunted V(E) and frequency responses to hypoxia. The results suggest that M(1) and M(3) muscarinic receptors play significant roles in the regulation of tidal volume at rest and that the afferent pathway originating from peripheral chemoreceptors involves M(3) receptors.
authors.affiliation: Neurobiologie Génétique et Intégrative, Institut de Neurobiologie Alfred Fessard, C.N.R.S., 91198 Gif-sur-Yvette, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Boudinot
authors.forename: Masahisa
authors.initials: M
authors.lastname: Yamada
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wess
authors.forename: Jean
authors.initials: J
authors.lastname: Champagnat
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Foutz
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002245:Carbon Dioxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010100:Oxygen / Q000494:pharmacology; D010993:Plethysmography, Whole Body / Q000379:methods; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D043643:Receptor, Muscarinic M1 / Q000235:genetics / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000502:physiology*; D012119:Respiration / Q000187:drug effects / Q000235:genetics*; D013990:Tidal Volume / Q000235:genetics / Q000502:physiology
chemical_list: D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D002245:Carbon Dioxide; D010100:Oxygen