Abstract
The hypoxic ventilatory response (HVR) comprises an initial increase in ventilation followed by a secondary depression. We tested the hypothesis that the exocytotic release of ATP by astrocytes in the preBötC attenuates this secondary depression via a P2Y1 receptor (R)‐mediated increase in ventilation. The preBötC of adult rats was injected with an adenovirus expressing tetanus toxin light chain (TeLC) and GFP under the control of the GFAP promoter. 7 days later rats were anesthetized and the HVR (10% O2, 5 min) measured via the phrenic nerve. Ventilation increased initially in the control group to 1.7±0.21 of baseline and then fell to 1.4±0.14. In the TeLC group, the HVR was significantly reduced during the initial (1.5± 0.08) and the secondary (1.2±0.05) phases. Unilateral injection of P2Y1R antagonist MRS2279 (500 µM) into the preBötC revealed that endogenous activation of P2Y1Rs significantly attenuated the secondary depression. Multiple second messenger blockers attenuated the frequency increase evoked by injection of a P2Y1R agonist MRS2365 (10μM) into the preBötC of rhythmic medullary slices of neonatal rats. These data suggest that during hypoxia, preBötC astrocytes release ATP, which binds to P2Y1Rs that act through PLC‐IP3‐gated Ca2+ release and PKC to increase ventilation. Supported by CIHR, AIHS, CFI, WCHRI, Wellcome Trust.
Published Version
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