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Okadaic Acid‐Sensitive Protein Phosphatases Constrain Phrenic Long‐Term Facilitation Following Sustained Hypoxia
Author(s) -
Wilkerson Julia ER,
BakerHerman Tracy L,
Mitchell Gordon S
Publication year - 2006
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.20.4.a372-a
Subject(s) - phosphatase , okadaic acid , hypoxia (environmental) , intermittent hypoxia , protein phosphatase 1 , respiratory system , medicine , biology , endocrinology , chemistry , pharmacology , phosphorylation , biochemistry , obstructive sleep apnea , organic chemistry , oxygen
Phrenic long‐term facilitation (pLTF) is a form of pattern‐sensitive respiratory plasticity induced by intermittent, but not sustained hypoxia (SH). The mechanism(s) underlying pattern‐sensitivity in pLTF is (are) unknown. Since certain protein phosphatases inhibit protein kinases, which are critical for multiple forms of neuroplasticity, including LTF, we hypothesized that protein phosphatase activation during sustained, but not intermittent, hypoxia confers pattern‐sensitivity to pLTF. To test the hypothesis that protein phosphatase activation constrains pLTF following SH, we intrathecally injected okadaic acid, a non‐specific protein phosphatase inhibitor (OA, 25nM, n=10), or vehicle (artificial CSF, n=9) over the C4 spinal cord in anesthetized, vagotomized, paralyzed and ventilated male Sprague‐Dawley rats prior to 25 min SH (11±1%O 2 ). 60 min post‐SH, integrated phrenic burst amplitude was significantly increased in OA‐treated versus vehicle‐treated rats (49±21% and 8±6% baseline, respectively, p < 0.05). pLTF in rats with OA and SH was indistinguishable from vehicle‐treated rats exposed to intermittent hypoxia (3, 5‐min 11±1%O 2 episodes; 50±11% baseline, n=11). Although a small frequency LTF was observed in all treatment groups, there were no significant differences between groups. These data suggest that protein phosphatases constrain pLTF expression when rats are exposed to SH, thereby contributing to pLTF pattern‐sensitivity. The relevant OA‐sensitive protein phosphatase remains to be identified. Supported by NIH HL89209, HL65383 and HL07654.