Back to Search Start Over

Phrenic Long-Term Facilitation Requires PKCθ Activity within Phrenic Motor Neurons

Authors :
Michael J. Devinney
Erica A. Dale
Timothy J. Peterson
Daryl P. Fields
Adrianne G. Huxtable
Gordon S. Mitchell
Publication Year :
2015
Publisher :
Society for Neuroscience, 2015.

Abstract

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.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....d58dd4ee8e08ce6d137aa149e38a2209