ATP sensitivity of preBotzinger complex neurones in neonatal rat in vitro:: mechanism underlying a P2 receptor-mediated increase in inspiratory frequency

P2 receptor (R) signalling plays an important role in the central ventilatory response to hypoxia. The frequency increase that results from activation of P2Y(1)Rs in the preBotzinger complex (preBotC; putative site of inspiratory rhythm generation) may contribute, but neither the cellular nor ionic mechanism(s) underlying these effects are known. We applied whole-cell recording to rhythmically-active medullary slices from neonatal rat to define, in preBotC neurones, the candidate cellular and ionic mechanisms through which ATP influences rhythm, and tested the hypothesis that putative rhythmogenic preBotC neurones are uniquely sensitive to ATP. ATP (1 mM) evoked inward currents in all non-respiratory neurones and the majority of respiratory neurons, which included inspiratory, expiratory and putative rhythmogenic inspiratory neurones identified by sensitivity to substance P (1 mu M) and DAMGO (50 mu M) or by voltage-dependent pacemaker-like activity. ATP current densities were similar in all classes of preBotC respiratory neurone. Reversal potentials and input resistance changes for ATP currents in respiratory neurones suggested they resulted from either inhibition of a K+ channel or activation of a mixed cationic conductance. The P2YR agonist 2MeSADP (1 mM) evoked only the latter type of current in inspiratory and pacemaker-like neurones. In summary, putative rhythmogenic preBotC neurones were sensitive to ATP. However, this sensitivity was not unique; ATP evoked similar currents in all types of preBotC respiratory neurone. The P2Y(1)R-mediated frequency increase is therefore more likely to reflect activation of a mixed cationic conductance in multiple types of preBotC neurone than excitation of one, highly sensitive group.