title: Okadaic acid-sensitive protein phosphatases constrain phrenic long-term facilitation after sustained hypoxia.
abstract: 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% O(2)). 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.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin 53706, USA. wilkersj@svm.vetmed.wisc.edu
authors.forename: Julia E R
authors.initials: JE
authors.lastname: Wilkerson
authors.forename: Irawan
authors.initials: I
authors.lastname: Satriotomo
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Baker-Herman
authors.forename: Jyoti J
authors.initials: JJ
authors.lastname: Watters
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019319:Okadaic Acid / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000502:physiology*; D010791:Phrenic Nerve / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019319:Okadaic Acid; C067024:okadaic acid-sensitive phosphatase; D010749:Phosphoprotein Phosphatases