title: Increased ventilation and CO2 chemosensitivity in acetylcholinesterase knockout mice.
abstract: To investigate the effects of a permanent excess of acetylcholine (AChE) on respiration, breathing and chemosensitivity were analyzed from birth to adulthood in mice lacking the AChE gene (AChE-/-), in heterozygotes, and in control wild-type (AChE+/+) littermates. Breathing at rest and ventilatory responses to brief exposures to hypoxia (10% O2) and hypercapnia (3-5% CO2) were measured by whole-body plethysmography. At rest AChE-/- mice show larger tidal volumes (VT, + 96% in adults), overall ventilation (VE, + 70%), and mean inspiratory flow (+270%) than wild-type mice, with no change in breathing frequency (fR). AChE-/- mice have a slightly blunted response to hypoxia, but increased VE and fR responses to hypercapnia. Heterozygous animals present no consistent alterations of breathing at rest and chemosensitivity is normal. Adult AChE-/- mice have an increased VE/VO2 and a marginally higher normalized VO2. The results suggest that the hyperventilation and altered chemosensitivity in AChE-/- mice largely reflect alterations of central respiratory control.
authors.affiliation: Neurobiologie Génétique et Intégrative, Institut de Neurobiologie Alfred Fessard, C.N.R.S., 91190 Gif-sur-Yvette, France.
authors.forename: E
authors.initials: E
authors.lastname: Boudinot
authors.forename: M J
authors.initials: MJ
authors.lastname: Emery
authors.forename: E
authors.initials: E
authors.lastname: Mouisel
authors.forename: A
authors.initials: A
authors.lastname: Chatonnet
authors.forename: J
authors.initials: J
authors.lastname: Champagnat
authors.forename: P
authors.initials: P
authors.lastname: Escourrou
authors.forename: A S
authors.initials: AS
authors.lastname: Foutz
mesh_terms: D000110:Acetylcholinesterase / Q000172:deficiency / Q000378:metabolism*; D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D005260:Female; D006935:Hypercapnia / Q000201:enzymology / Q000503:physiopathology*; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000502:physiology; D012123:Pulmonary Ventilation / Q000502:physiology*; D012119:Respiration; D015656:Respiratory Mechanics / Q000502:physiology*
chemical_list: D002245:Carbon Dioxide; D000110:Acetylcholinesterase