P2 receptors modulate respiratory rhythm but do not contribute to central CO2 sensitivity in vitro

Multiple brainstem sites are proposed to contribute to central respiratory chemosensitivity, however, the underlying molecular mechanisms remain unknown. P2X₂ subunit-containing ATP receptors, which mediate pH-sensitive currents, appear to contribute to central chemosensitivity in vivo [J. Physiol. 523 (2000) 441]. However, recent data from P2X₂ knockout mice [J. Neurosci. 23 (2003) 11315] indicate that they are not essential. To further explore the role of P2 receptors in central chemosensitivity, we examined the effects of P2 receptor agonists/antagonists on respiratory-related activity and CO₂-sensitivity of rhythmically-active in vitro preparations from neonatal rat. Our main findings: (i) that putative chemosensitive regions of the ventrolateral medulla are immunoreactive for the P2X₂ subunit; (ii) that ATP potentiates respiratory frequency in a dose-dependent, and PPADS-sensitive (P2 receptor antagonist), manner; and (iii) that the increase in burst frequency produced by increasing CO₂ is unaffected by PPADS, indicate that ATP is a potent modulator of respiratory activity, but that P2 receptors do not contribute to central chemosensitivity in vitro.