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Spinal AMP kinase activity differentially regulates phrenic motor plasticity
Raphael Rodrigues Perim1, Daryl P Fields1, Gordon S Mitchell1
1Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, Florida.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|January 24, 2020
Summary
Spinal AMP-activated protein kinase (AMPK) differentially regulates respiratory plasticity. AMPK activation blocks serotonin 7 receptor-induced plasticity but not serotonin 2A receptor-induced plasticity, revealing a key metabolic control mechanism.
Area of Science:
- Neuroscience
- Physiology
- Cellular Biology
Background:
- Acute intermittent hypoxia (AIH) induces phrenic motor plasticity through distinct cellular pathways.
- Moderate AIH uses serotonin 2A (5-HT2A) receptors, ERK, and BDNF.
- Severe AIH utilizes serotonin 7 (5-HT7) receptors, Akt, mTOR, and TrkB, linked to adenosine signaling.
Purpose of the Study:
- To investigate the role of spinal AMP-activated protein kinase (AMPK) in differentially regulating phrenic motor plasticity (pMF) induced by 5-HT2A and 5-HT7 receptors.
- To test the hypothesis that AMPK, a known mTOR inhibitor, differentially affects pMF mediated by distinct serotonin receptor pathways.
Main Methods:
- Administered 5-HT2A or 5-HT7 receptor agonists intrathecally in rats.
- Recorded phrenic nerve activity in anesthetized, paralyzed, and ventilated rats.
- Utilized AMPK activators (2-deoxyglucose, metformin) and an AMPK inhibitor (compound C) to assess effects on pMF.
Main Results:
- Spinal AMPK activation blocked 5-HT7 receptor-induced pMF but not 5-HT2A receptor-induced pMF.
- Inhibition of 5-HT7 receptor-induced pMF by AMPK activators was reversed by the AMPK inhibitor compound C.
- These findings indicate AMPK differentially regulates cellular mechanisms underlying serotonin-induced phrenic motor plasticity.
Conclusions:
- AMPK acts as a differential regulator of serotonin-mediated phrenic motor plasticity.
- Metabolic challenges influencing AMPK activity may selectively impact specific forms of respiratory motor plasticity.
- Targeting AMPK could offer a strategy to modulate respiratory plasticity under specific conditions.
