P2Y1 receptor‐mediated potentiation of XII motoneuron (MN) inspiratory motor output in neonatal rat

Abstract

Inspiratory rhythm generating networks in the preBötzinger Complex (preBötC) are ~100‐fold more sensitive to ATP than XII MNs that control airway patency. This is believed to reflect in part that the effects of ATP in the preBötC are primarily mediated by P2Y1Rs while P2XRs receptors dominate the actions of ATP in XII MNs. However, the effects of P2Y1R signaling on XII motor output and MN properties have not been examined. To address this deficit, we applied nerve and whole‐cell recording techniques to rhythmic medullary slices of neonatal rat.Local application of MRS2365 (P2Y1R agonist) to the XII nucleus of rhythmic slices increased tonic discharge and evoked 22±2 (0.1 mM) and 33±4% (1 mM, n=16) increases in inspiratory burst amplitude. MRS2365 also increased the frequency and amplitude of spontaneous PSCs in non‐inspiratory and inspiratory MNs alike. In inspiratory MNs, it also increased the charge transferred per inspiratory cycle (12±6%, n=5). The increase in synaptic activity was superimposed on a small, slow, inward current that was similar in all XII MNs, averaging 27±7 pA (1 mM, n=10). Following block action potentials with TTX, MRS2365 had no effect on membrane current or resistance.These data suggest that P2Y1Rs do not directly affect XII MN membrane properties, but potentiate inspiratory XII nerve output by specifically modulating synaptic function.Supported by CIHR, NSERC, CIHR‐MFN, AHFMR, CFI, ASRA.