Spinal activation of protein kinase C elicits phrenic motor facilitation

Respir Physiol Neurobiol, 2018 · DOI: 10.1016/j.resp.2017.10.007 · Published: October 1, 2018

Simple Explanation

This study investigates how activating a group of enzymes called protein kinase C (PKC) in the spinal cord affects breathing muscles. Specifically, it looks at the phrenic nerve, which controls the diaphragm, the main muscle for breathing. The researchers found that activating PKC in the spinal cord of rats increased the activity of the phrenic nerve, leading to stronger contractions of the diaphragm. This effect was blocked when they used drugs to inhibit PKC, confirming that PKC activation was responsible for the increased nerve activity. This suggests that targeting specific PKC enzymes in the spinal cord could be a way to improve breathing in conditions like spinal cord injury or diseases that weaken breathing muscles.

Study Duration

Not specified

Participants

Adult (12–17 week old) male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Spinal PKC activation via intrathecal PMA elicits pMF.
2
PMA-induced pMF requires PKC activation.
3
PMA elicits pMF by activating classical/novel PKC isoforms.

Research Summary

This study demonstrates that spinal PKC activation elicits pMF, an effect prevented by pretreatment with two PKC inhibitors that differ in their mechanism of action and isoform specificity: BIS and NPC. These findings rule out contributions from either PKCθ or the atypical PKCs since NPC does not block PKCθ-dependent pMF, and PMA does not activate atypical PKC isoforms. Although the specific PKC isoforms involved are not certain based on our studies, they must represent conventional or novel PKC isoforms that have not previously been implicated in phrenic motor plasticity.

Practical Implications

Therapeutic Potential

Understanding PKC's role in respiratory plasticity may lead to new treatments for breathing disorders.

Targeted Drug Development

Identifying specific PKC isoforms involved could allow for more targeted and effective drug therapies.

Rehabilitation Strategies

Harnessing respiratory motor plasticity could improve outcomes in spinal cord injury and other motor deficits.

Study Limitations

1
Specific PKC isoforms involved are not certain.
2
Study conducted on anesthetized rats may not fully translate to awake humans.
3
The precise mechanisms downstream from PKC activation remain to be elucidated.

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