Sensing arterial CO(2) levels: a role for medullary P2X receptors

ATP has been shown to act as an excitatory neurotransmitter in the central nervous system. In this review, evidence is presented to indicate that when ATP is micro-injected into the ventrolateral medulla (VLM) of the rat, changes in respiratory activity are elicited. These effects, and accompanying changes in heart rate and blood pressure are mediated by P2X purinoreceptors. Immunocytochemistry indicates a prevalence of P2X(2) and P2X(6) purinoreceptors in this region of the medulla. The P2 purinoceptor antagonists, suramin and PPADS blunt the respiratory responses to changes in arterial CO(2) levels when micro-injected into the VLM. This effect is shown electrophysiologically to be mediated by purinoreceptors located primarily on respiratory neurones of the VLM including the Bötzinger complex. As the effects of agonist activation of P2X(2) purinoceptors expressed in HEK293 cells and Xenopus oocytes are potentiated by lowering pH, these data imply that the central respiratory response to CO(2) depends in part on the pH sensitivity of purinoreceptors located on inspiratory neurones. The implications for respiratory activity and control are discussed.