Phrenic long-term facilitation requires PKCθ activity within phrenic motor neurons.

Journal Article (Journal Article)

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons.

Full Text

Duke Authors

Cited Authors

  • Devinney, MJ; Fields, DP; Huxtable, AG; Peterson, TJ; Dale, EA; Mitchell, GS

Published Date

  • May 27, 2015

Published In

Volume / Issue

  • 35 / 21

Start / End Page

  • 8107 - 8117

PubMed ID

  • 26019328

Pubmed Central ID

  • PMC4444536

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.5086-14.2015


  • eng

Conference Location

  • United States