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% CO2) 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)over dot>(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)over dot>(E) and V-T at rest, a reduced V-T response slope to hypercapnia, and blunted <(V)over dot>(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. (C) 2003 Elsevier B.V. All rights reserved.