Premium
ATP acts via P2Y1 receptors in the preBötzinger Complex in vivo to attenuate the secondary hypoxic respiratory depression
Author(s) -
Rajani Vishaal,
Zwicker Jennifer D.,
Pagliardini Silvia,
Funk Gregory D.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1137.16
Subject(s) - respiratory system , receptor , purinergic receptor , ventilation (architecture) , medicine , respiratory center , endocrinology , anesthesia , respiration , hypoxia (environmental) , chemistry , biology , anatomy , mechanical engineering , organic chemistry , oxygen , engineering
The ventilatory response to hypoxia comprises an initial increase in ventilation followed by a secondary depression that can be life‐threatening in premature infants. The mechanisms underlying the kinetics and magnitude of this secondary depression are not known, but ATP released within the ventrolateral medulla acts via purinergic (P2) receptors to attenuate this depression. We explored the hypothesis developed from analysis of the rhythmic medullary slice preparation that ATP acts via P2Y 1 receptors in the preBötzinger Complex (preBötC, a critical site for inspiratory rhythm generation) to mediate this attenuation. Adult, urethane‐anesthetized, spontaneously‐breathing, vagotomized rats were exposed to 10% O 2 (90% N 2 ) for 5 min immediately following local unilateral injection of vehicle (0.2μl HEPES buffer) or 500 μM MRS2279 (P2Y 1 receptor antagonist) into the preBötC. Respiratory frequency (f R ) and minute ventilation (V E ) increased rapidly by ~40% in both groups. f R fell to baseline levels in the control group but to 0.8 of baseline in the MRS2279‐injected animals. V E fell to levels that were 20% above baseline in the control group but to baseline in the MRS2279 group. Data suggest that during hypoxia endogenously‐released ATP acts via P2Y 1 receptors in the preBötC to reduce the magnitude of the secondary hypoxic respiratory depression. Supported by CIHR, AIHS, CFI, WCHRI and ALA.