Ventilatory pattern and chemosensitivity in M1 and M3 muscarinic receptor knockout mice.
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.
Boudinot
Eliane
E
Neurobiologie Génétique et Intégrative, Institut de Neurobiologie Alfred Fessard, C.N.R.S., 91198 Gif-sur-Yvette, France.
Yamada
Masahisa
M
Wess
Jürgen
J
Champagnat
Jean
J
Foutz
Arthur S
AS
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
D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D002245:Carbon Dioxide; D010100:Oxygen