Abstract
The respiratory rhythm response to the afferent inputs from the pulmonary stretch receptors depends critically on the discharge frequency of afferent fibers. (Takano and Kato, J. Physiol., 1999, 2003). P2X receptors modulate excitatory syn-aptic transmission in the nucleus of the solitary tract (NTS) in a manner sensitive to pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS; Kato and Shige-tomi, J. Physiol., 2001). To analyze how P2X receptors in the NTS participate in the frequency-dependent switching of the effect of vagal afferent inputs, we locally injected PPADS (20 nmole/ side/rabbit) into unilateral NTS in anesthetized rabbits. In the side of PPDAS injection, the inspiratory pro-motion by low frequency vagus nerve stimulation (20 Hz) was significantly attenuated for 120 min after injection, whereas the inspiratory suppression by high-frequency stimulation (160 Hz) remained unchanged. The effects of both low- and high- frequency stimulation of the vagus nerve remained in-tact in the side in which vehicle (PBS) was injected. The ex-tent of the injected drug diffusion in the brain stem, as confirmed with Evans blue staining, was limited within a ra-dius of 1 mm, showing that the frequency-dependent influence of PPADS was mediated by its effect on the NTS network. These results suggest that the ATP-P2X receptor-mediated transmission in the NTS plays critical roles in the afferent frequency-dependent responses of the central respiratory pat-tern generator. [J Physiol Sci. 2007;57 Suppl:S213]