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Spinal protein phosphatase 1 constrains respiratory plasticity after sustained hypoxia (1091.2)
Author(s) -
Huxtable Adrianne,
Peterson Timothy,
Kopp Elizabeth,
Mitchell Gordon
Publication year - 2014
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.28.1_supplement.1091.2
Subject(s) - small interfering rna , hypoxia (environmental) , phosphatase , protein phosphatase 2 , okadaic acid , gene knockdown , biology , protein phosphatase 1 , intermittent hypoxia , acid phosphatase , pharmacology , anesthesia , chemistry , medicine , microbiology and biotechnology , phosphorylation , biochemistry , rna , enzyme , gene , oxygen , organic chemistry , obstructive sleep apnea
Plasticity is an important aspect of the neural control of breathing. One well‐studied form of respiratory plasticity is phrenic long‐term facilitation (pLTF) induced by acute intermittent, but not sustained hypoxia. pLTF pattern sensitivity partially reflects differential regulation by okadaic acid‐sensitive protein phosphatases (PP) during intermittent vs. sustained hypoxia (Wilkerson et al., J Neurosci, 2008), although the relevant phosphatase has not been identified. Here, we show that pLTF is revealed after sustained hypoxia (25 min, 10.5% O2) in rats pre‐treated with bilateral intrapleural injections of small interfering RNAs (siRNAs, Accell‐modified, Thermoscientific; 30 μl/side, 3.33 μM, 3 days) targeting PP1 mRNA (40±14% baseline, n=4). siRNAs targeting PP2A (10±13%, n=3), PP5 (12±13%, n=4) and non‐targeting siRNAs (‐1±11%, n=5) had no effect. siRNAs had no effect on the response during hypoxia. Preliminary immunohistochemistry confirms a small knockdown of targeted phosphatases within the phrenic motor nucleus. PP1 appears to be the relevant okadaic acid‐sensitive phosphatase regulating pLTF. Grant Funding Source : Supported by: HL111598, HL080209, Francis Family Foundation (AGH).