Increased ventilation and CO2 chemosensitivity in acetylcholinesterase knockout mice

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+/+) littermazes. Breathing at rest and ventilatory responses to brief exposures to hypoxia (10% O-2) and hypercapnia (3-5% CO2) were measured by whole-body plethysmography. At rest AChE-/- mice show larger tidal volumes (V-T, + 96% in adults), overall ventilation (V-E, + 70%), and mean inspiratory flow (+270%) than wild-type mice, with no change in breathing frequency (f(R)). AChE-/- mice have a slightly blunted response to hypoxia, but increased V-E and f(R) responses to hypercapnia. Heterozygous animals present no consistent alterations of breathing at rest and chemosensitivity is normal. Adult AChE-/mice have an increascd V-E/V-O2 and a marginally higher normalized V-O2. The results suggest that the hyperventilation and altered chemosensitivity in AChE-/- mice largely reflect alterations of central respiratory control. (C) 2004 Elsevier B.V. All rights reserved.