Purinergic P2 receptors modulate excitability but do not mediate pH sensitivity of RTN respiratory chemoreceptors.
The cellular mechanism(s) by which the brain senses changes in pH to regulate breathing (i.e., central chemoreception) have remained incompletely understood, in large part because the central respiratory chemoreceptors have themselves eluded detection. Here, we recorded from a newly identified population of central chemoreceptors located in the retrotrapezoid nucleus (RTN) on the ventral surface of the brainstem to test a recently proposed role for purinergic P2 receptor signaling in central respiratory chemoreception (Gourine et al., 2005). Using loose-patch current-clamp recordings in brainstem slices from rat pups (postnatal day 7-12), we indeed show purinergic modulation of pH-sensitive RTN neurons: activation of P2X receptors indirectly inhibited RTN firing by increasing inhibitory input, whereas P2Y receptor stimulation caused direct excitation of RTN chemoreceptors. However, after blocking P2 receptors with the broad-spectrum antagonists PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate) or RB2 (reactive blue 2), the pH sensitivity of RTN neurons remained intact. Therefore, we conclude that purinergic signaling can modulate RTN neuron activity but does not mediate the pH sensing intrinsic to these central respiratory chemoreceptors.
Mulkey
Daniel K
DK
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. dm5up@virginia.edu
Mistry
Akshitkumar M
AM
Guyenet
Patrice G
PG
Bayliss
Douglas A
DA
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011522:Protons; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012125:Respiratory Center / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D003292:Convulsants; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D011522:Protons; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014227:Triazines; D002245:Carbon Dioxide; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C022571:adenosine 5'-O-(3-thiotriphosphate); C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D013331:Strychnine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D014544:Uridine Triphosphate; D001640:Bicuculline