To identify muscarinic acetylcholine receptor (mAChR) subtypes being involved in the respiratory control system, we analyzed respiratory function of each subtype (M1-M5) of mAChRs gene knockout mice. Ventilatory parameters, i.e. respiratory frequency, tidal volume and minute ventilation, were recorded by whole body plethysmography in normoxic, hyperoxic, hypoxic, and hypercapnic conditions. In a single subtype of mAChR knockout mice, respiratory parameters in each condition did not differ from those of wild type mice. In contrast, respiratory frequency (138 ± 24 breaths/min) of M1/M3-compound knockout mice was significantly lower than that (180 ± 33 breaths/min) of wild type mice under normoxia. This slow rhythm of breathing in the compound knockout mice was observed under hyperoxia and hypercapnia but not under hypoxia. Tidal volume of M1/M3-compound knockout mice in each condition was slightly smaller than that of wild type mice, although the difference was not statistically significant We conclude that M1/M3-compound subtypes of mAChRs play a significant role in the respiratory neural network.
This work was supported by Industrial Technology Research Grant Program from the New Energy and Industrial Technology Development Organization of Japan (M.M.). [Jpn J Physiol 54 Suppl:S111 (2004)]