Okadaic acid-sensitive protein phosphatases constrain phrenic long-term facilitation after sustained hypoxia

Julia E R Wilkerson, Irawan Satriotomo, Tracy L. Baker-Herman, Jyoti J. Watters, Gordon S. Mitchell

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Phrenic long-term facilitation (pLTF) is a serotonin-dependent form of pattern-sensitive respiratory plasticity induced by intermittent hypoxia (IH), but not sustained hypoxia (SH). The mechanism(s) underlying pLTF pattern sensitivity are unknown. SH and IH may differentially regulate serine/threonine protein phosphatase activity, thereby inhibiting relevant protein phosphatases uniquely during IH and conferring pattern sensitivity to pLTF. We hypothesized that spinal protein phosphatase inhibition would relieve this braking action of protein phosphatases, thereby revealing pLTF after SH. Anesthetized rats received intrathecal (C4) okadaic acid (25 nM) before SH (25 min, 11% O 2). Unlike (vehicle) control rats, SH induced a significant pLTF in okadaic acid-treated rats that was indistinguishable from rats exposed to IH (three 5 min episodes, 11% O2). IH and SH with okadaic acid may elicit pLTF by similar, serotonin-dependent mechanisms, because intravenous methysergide blocks pLTF in rats receiving IH or okadaic acid plus SH. Okadaic acid did not alter IH-induced pLTF. In summary, pattern sensitivity in pLTF may reflect differential regulation of okadaic acid-sensitive serine/threonine phosphatases; presumably, these phosphatases are less active during/after IH versus SH. The specific okadaic acid-sensitive phosphatase(s) constraining pLTF and their spatiotemporal dynamics during and/or after IH and SH remain to be determined.

Original languageEnglish (US)
Pages (from-to)2949-2958
Number of pages10
JournalJournal of Neuroscience
Issue number11
StatePublished - Mar 12 2008


  • Control of breathing
  • Hypoxia
  • Motor neuron
  • Pattern
  • Phosphatase
  • Plasticity

ASJC Scopus subject areas

  • General Neuroscience


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