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Severe sustained hypoxia elicits long‐lasting phrenic motor facilitation (pMF) by an adenosinergic mechanism
Author(s) -
Nichols Nicole L,
Devinney Michael J,
Mitchell Gordon S
Publication year - 2012
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.26.1_supplement.704.8
Subject(s) - intermittent hypoxia , adenosine , hypoxia (environmental) , facilitation , adenosine receptor , respiratory system , receptor , medicine , endocrinology , anesthesia , chemistry , pharmacology , biology , neuroscience , agonist , oxygen , organic chemistry , obstructive sleep apnea
Moderate acute intermittent hypoxia (AIH; 3, 5‐min episodes) elicits serotonin‐dependent phrenic long‐term facilitation (pLTF); this form of pLTF is enhanced by spinal adenosine 2A (A 2A ) receptor inhibition. Severe AIH also elicits pLTF, but via an adenosine A 2A receptor dependent (serotonin independent) mechanism. This shift may reflect greater spinal adenosine release/formation during severe AIH. Moderate sustained hypoxia (SH; 9–20‐min) fails to elicit pMF, demonstrating pMF pattern‐sensitivity. However, since severe SH may increase extracellular adenosine levels, we hypothesized that severe SH would elicit pMF via an A 2A receptor dependent mechanism. Severe SH (PaO 2 =25–35; 25 min) was studied in anesthetized, paralyzed and ventilated rats +/− spinal A 2A receptor inhibition (MSX‐3, i.t., C 4 ). Severe SH elicits pMF (53%±12% at 60 min post‐SH) vs . time controls (10%±3%; p<0.05, both n=8). MSX‐3 pre‐treatment attenuated severe SH induced pMF (10%±5%; p<0.05, n=7). Thus, severe SH and AIH both elicit spinal A 2A ‐dependent pMF, unlike moderate SH and AIH (Devinney et al., ibid ), indicating that adenosine‐dependent pMF is not pattern sensitive. Understanding mechanisms of pattern sensitivity in respiratory plasticity may enable us to “harness” plasticity as a treatment for respiratory insufficiency. [Supported by NIH HL080209 and T32 007654 and the Francis Families Foundation]