Chemosensory control by purinergic signaling within the retrotrapezoid nucleus (RTN) in conscious rats

Abstract

The RTN contains a population of CO2/H+‐sensitive neurons that send excitatory projections to respiratory centers to regulate breathing (i.e., chemoreceptors). Evidence also suggests that ATP, possibly released by astrocytes, is an important mediator of RTN chemoreceptor activity. However, this possibility has yet to be tested in conscious animals. The goal of this study is to determine if purinergic signaling in the RTN contributes to breathing under resting conditions and during central chemoreflex activation in unrestrained awake rats. Male Wistar rats (280–300 g) with bilateral stainless steel cannulas implanted into the RTN were used. Bilateral RTN injections of PPADS (P2‐receptor antagonist: 5 mM ‐ 50 nl) did not change baseline minute ventilation (VE), mean arterial pressure (MAP), or heart rate (HR). However, PPADS treated animals exhibited reduced tidal volume (VT) (6.6 ± 0.14 vs. saline: 9.1 ± 1.4 ml/kg) and VE (748 ± 2.5 vs. saline: 1257 ± 239 ml/kg/min) responses to hypercapnia (7% CO2). CO2‐induced changes in respiratory frequency, MAP and HR were not affected by PPADS. These results suggest that CO2‐evoked ATP release in the RTN contributes to control of breathing in conscious animals