ATP as a mediator of mammalian central CO 2 chemoreception

1 A role for P2 purinoceptors in the chemosensory response of respiratory neurones localised in the ventrolateral medulla to changes in arterial CO 2 levels was investigated in the anaesthetised rat. Extracellular recordings were made from different classes of respiratory neurone and the effects of P2 receptor blockade on CO 2 ‐evoked changes in activity investigated. 2 Increasing inspired CO 2 excited 85 % of inspiratory neurones in the pre‐Bötzinger complex. In all cases, CO 2 ‐evoked excitation was blocked by ionophoretic application of the P2receptor antagonists suramin (0·02 M) and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS; 100 μM), but not the adenosine receptor antagonist 8‐phenyltheophylline (8‐PT; 100 μM). Suramin and PPADS often reduced ongoing activity, and blocked the excitatory effects of ATP. Inspiratory neurones were also excited by the P2X receptor agonist αβ‐methyleneATP, suggesting a specific role for P2X receptors. 3 Sixty‐six per cent of pre‐inspiratory neurones were also excited by CO 2 . This effect was reduced or abolished by prior application of P2 receptor antagonists. Although post‐inspiratory and expiratory neurones were excited by increasing levels of CO 2 , and also by ionophoretically applied ATP, the CO 2 ‐evoked effects were unaffected by P2 receptor blockade. 4 We suggest that ATP, possibly acting via P2X purinoceptors localised within the ventral respiratory group, is involved in central chemoreception. Specifically, these distinctive CO 2 ‐P2X‐mediated actions were observed only in inspiratory neurones (incrementing inspiratory neurones and pre‐inspiratory neurones), which appear to have purinoceptors with pH sensitivity that can account for the actions of CO 2 in modifying ventilatory activity.