Spinal activation of protein kinase C elicits phrenic motor facilitation.

Published

Journal Article

The protein kinase C family regulates many cellular functions, including multiple forms of neuroplasticity. The novel PKCθ and atypical PKCζ isoforms have been implicated in distinct forms of spinal, respiratory motor plasticity, including phrenic motor facilitation (pMF) following acute intermittent hypoxia or inactivity, respectively. Although these PKC isoforms are critical in regulating spinal motor plasticity, other isoforms may be important for phrenic motor plasticity. We tested the impact of conventional/novel PKC activator, phorbol 12-myristate 13-acetate (PMA) on pMF. Rats given cervical intrathecal injections of PMA exhibited pMF, which was abolished by pretreatment of broad-spectrum PKC inhibitors bisindolymalemide 1 (BIS) or NPC-15437 (NPC). Because PMA fails to activate atypical PKC isoforms, and NPC does not block PKCθ, this finding demonstrates that classical/novel PKC isoforms besides PKCθ are sufficient to elicit pMF. These results advance our understanding of mechanisms producing respiratory motor plasticity, and may inspire new treatments for disorders that compromise breathing, such as ALS, spinal injury and obstructive sleep apnea.

Full Text

Duke Authors

Cited Authors

  • Devinney, MJ; Mitchell, GS

Published Date

  • October 2018

Published In

Volume / Issue

  • 256 /

Start / End Page

  • 36 - 42

PubMed ID

  • 29081358

Pubmed Central ID

  • 29081358

Electronic International Standard Serial Number (EISSN)

  • 1878-1519

Digital Object Identifier (DOI)

  • 10.1016/j.resp.2017.10.007

Language

  • eng

Conference Location

  • Netherlands