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J Physiol Volume 586, Number 5, 1429-1446, March 1, 2008 DOI: 10.1113/jphysiol.2007.143024
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RESPIRATORY

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

 A. R. Lorier1,2, J. Lipski2, G. D. Housley2, J. J. Greer1 and G. D. Funk1,2

1 Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7
2 Department of Physiology, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

P2 receptor (R) signalling plays an important role in the central ventilatory response to hypoxia. The frequency increase that results from activation of P2Y1Rs in the preBötzinger complex (preBötC; 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 preBötC neurones, the candidate cellular and ionic mechanisms through which ATP influences rhythm, and tested the hypothesis that putative rhythmogenic preBötC 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 µM) and DAMGO (50 µM) or by voltage-dependent pacemaker-like activity. ATP current densities were similar in all classes of preBötC 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 preBötC neurones were sensitive to ATP. However, this sensitivity was not unique; ATP evoked similar currents in all types of preBötC respiratory neurone. The P2Y1R-mediated frequency increase is therefore more likely to reflect activation of a mixed cationic conductance in multiple types of preBötC neurone than excitation of one, highly sensitive group.

(Received 15 August 2007; accepted after revision 31 December 2007; first published online 3 January 2008)
Corresponding author G. D. Funk: 7–50 Medical Sciences Building, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7. Email: gf{at}ualberta.ca






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