RT Journal Article
SR Electronic
T1 Okadaic Acid-Sensitive Protein Phosphatases Constrain Phrenic Long-Term Facilitation after Sustained Hypoxia
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2949
OP 2958
DO 10.1523/JNEUROSCI.5539-07.2008
VO 28
IS 11
A1 Julia E. R. Wilkerson
A1 Irawan Satriotomo
A1 Tracy L. Baker-Herman
A1 Jyoti J. Watters
A1 Gordon S. Mitchell
YR 2008
UL http://www.jneurosci.org/content/28/11/2949.abstract
AB 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% O2). 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.